HGNC Approved Gene Symbol: TRBC1
Cytogenetic location: 7q34 Genomic coordinates (GRCh38): 7:142,791,694-142,793,141 (from NCBI)
T-lymphocytes recognize antigens via a mechanism that resembles that used by immunoglobulins (Igs; see 147200) produced by B cells. There are 2 main mature T-cell subtypes, those expressing alpha (see TRAC; 186880) and beta chains, and those expressing gamma (see TRGC1; 186970) and delta (see TRDC; 186810) chains. Unlike secreted Ig molecules, T-cell receptor chains are membrane bound and act through cell-cell contact. The genes encoding the T-cell receptor beta chain are clustered on chromosome 7. The T-cell receptor beta chain is formed when 1 of 52 variable (V) genes (see 615446), which encode the N-terminal antigen recognition domain, rearranges to a diversity (D) gene and a joining (J) gene to create a functional V region exon that is transcribed and spliced to a constant (C) region gene segment encoding the C-terminal portion of the molecule. Unlike the alpha chain locus, the beta chain locus has 2 separate clusters of genes after the V genes, each containing a D gene (e.g., TRBD1; 615447), several J genes (see 615449), and a C gene. The 2 C genes, TRBC1 and TRBC2 (615445), encode highly homologous products with no functional differences. The lymphoid-specific proteins RAG1 (179615) and RAG2 (179616) direct the V(D)J recombination process in both T and B cells. Following synthesis, the alpha and beta chains pair to yield the alpha-beta T-cell receptor heterodimer (Janeway et al., 2005).
Pestano et al. (1999) identified a differentiative pathway taken by CD8 cells bearing receptors that cannot engage class I MHC (see 142800) self-peptide molecules because of incorrect thymic selection, defects in peripheral MHC class I expression, or antigen presentation. In any of these cases, failed CD8 T-cell receptor coengagement results in downregulation of genes that account for specialized cytolytic T-lymphocyte function and resistance to cell death (CD8-alpha/beta, see 186730; granzyme B, 123910; and LKLF, 602016), and upregulation of Fas (134637) and FasL (134638) death genes. Thus, MHC engagement is required to inhibit expression and delivery of a death program rather than to supply a putative trophic factor for T cell survival. Pestano et al. (1999) hypothesized that defects in delivery of the death signal to these cells underlie the explosive growth and accumulation of double-negative T cells in animals bearing Fas and FasL mutations, in patients that carry inherited mutations of these genes, and in about 25% of systemic lupus erythematosus patients that display the cellular signature of defects in this mechanism of quality control of CD8 cells.
Lee et al. (2002) assessed TCR-mediated tyrosine kinase signaling in the immature and mature immunologic synapses of naive CD4 (186940)-positive T cells and antigen-presenting cells (APCs) using mouse splenocytes. Confocal and differential interference contrast microscopy demonstrated that the adhesion molecule LFA1 (153370/600065) is localized at the center of immature synapses, while antibody to TCR V-beta-3 indicated that TCRs are concentrated at the synapse periphery. TCR-regulated active tyrosine kinase signaling by LCK (153390) and then by ZAP70 (176947) occurs in the periphery of the immature immunologic synapse and largely abates before the mature immunologic synapse forms. Lee et al. (2002) proposed that the immunologic synapse is involved in TCR downregulation and endocytosis. In a commentary, van der Merwe and Davis (2002) instead proposed that the synapse is linked to the integration of non-TCR signaling and polarized secretion of cytokines by T cells.
Using confocal microscopy, Maldonado et al. (2004) found a random distribution of Tcrb, Il4r (147781), and Ifngr1 (107470) in fixed and permeabilized mouse naive T-helper lymphocytes (Thp) conjugated with mouse mature splenic dendritic cells (DCs). In cells fixed and permeabilized 30 minutes after conjugation of Thp and antigen-loaded DCs, the authors observed a calcium- and Ifng (147570)-dependent colocalization of Tcrb and Ifngr1, but not Il4r, at the Thp-DC interface. This observation was more apparent in the Th1-prone C57Bl/6 mouse strain than in the Th2-prone BALB/c strain. In the presence of Il4 (147780), but not Il10 (124092), Ifngr1 migration and copolarization was completely inhibited. In mice lacking the Il4r signaling molecule, Stat6 (601512), prevention of Tcrb/Ifngr1 copolarization was abolished. Maldonado et al. (2004) proposed that strong TCR signaling leads to accentuated IFNGR copolarization and the assembly of a Th1 signalosome, which is further stabilized by secretion of IFNG, unless an inhibitory signal, such as IL4 secretion and STAT6 activation, occurs and leads to the assembly of a Th2 signalosome. They concluded that the immunologic synapse may be involved in the control of cell fate decisions.
Teixeiro et al. (2009) generated OT-1 TCR transgenic mice with ovalbumin peptide-specific T cells and a point mutation in the TCRB transmembrane domain resulting in replacement of the most C-terminal tyr in the conserved antigen receptor transmembrane (CART) motif with leu. The TCR in wildtype and mutant T cells recognized and responded to ligands equivalently in terms of phenotype, kinetics, and function, except for defective Fasl expression in the mutant cells. However, mutant mice showed eventual loss of detectable memory Cd8-positive T cells, and mutant memory T cells were defective in their ability to mount secondary responses. Cells with an ala-to-asn mutation at residue 16 in the CART motif exhibited the same phenotype. ELISA and confocal microscopy demonstrated impaired Nfkb (see 164011) induction and failure of the mutant TCR to properly polarize to the immunologic synapse. Teixeiro et al. (2009) concluded that the mutant T cells differentiated into effector T cells normally but had defective memory development. The results were consistent with a 2-lineage model in which memory or effector development is determined early during the immune response by coordinating the recruitment of fate-determining proteins at the level of the immunologic synapse.
Scott-Browne et al. (2009) demonstrated that specific germline-encoded amino acids in the TCR promote 'generic' MHC recognition and control thymic selection. In mice expressing single, rearranged TCR beta-chains, individual mutation of amino acids in the complementarity-determining region 2-beta to ala reduced development of the entire TCR repertoire. Scott-Browne et al. (2009) concluded that thymic selection is controlled by germline-encoded MHC contact points in the alpha-beta TCR, and that the diversity of the peripheral T-cell repertoire is enhanced by this built-in specificity.
Brennan et al. (2012) examined CD8-positive T-cell responses to an HLA-B7 (see 142830)-restricted epitope of the 65-kD cytomegalovirus phosphoprotein antigen recognized by a public TCR beta chain encoded by the variable gene segment TBRV4-3, which is frequently deleted in all major ethnic groups. Individuals homozygous for the TBRV4-3 deletion retained a significant response to the epitope, but the unavailability of the dominant public TCR led to the deployment of a broad array of alternative TCRs, thereby enhancing antiviral immune control across the population. The findings suggested that repertoire diversity generated in the absence of the dominant public TCR may lead to better protection from viral escape mutation.
By automated, high-throughput sequence analysis of gene usage, length, encoded amino acid sequence, and sequence diversity of the complementarity determining region-3 of T-cell receptor beta chain, followed by complexity scoring, Krell et al. (2013) distinguished between aplastic anemia, hepatitis-induced anemia, and healthy controls. They concluded that next-generation sequencing-spectratyping allows in-depth analysis of T-cell receptor repertoires and their restriction in clinical samples.
Rowen et al. (1996) sequenced the TCRB 'locus' on chromosome 7, which comprises a complex family of genes. The locus was found to contain 2 types of coding elements: TCR elements (65 variable gene segments and 2 clusters of diversity, joining, and constant segments) and 8 trypsinogen genes (e.g., 276000). These coding elements constitute 4.6% of the DNA of the locus. The total sequence was 685 kb in length.
Rowen et al. (1996) characterized the organization and structures of all of the TCRB elements; 19 pseudogenes and 22 relics could be readily differentiated from the 46 functional genes by computational approaches. Their identification of 8 trypsinogen genes raised a question as to whether their association arose from functional or regulatory constraints, or is inadvertent. They found that a portion of the TCRB locus has been duplicated and translocated from chromosome 7 to chromosome 9, which suggested a possible mechanism for the creation of new multigene families. The extent of sequence variation (polymorphism) within the locus is high. At least 30% of the TCRB locus is composed of genomewide interspersed repeats, but these do not appear to facilitate the duplication of locus-specific repeats. Eight locus-specific repeats (homology units) have duplicated in a tandem or dispersed manner. Rowen et al. (1996) claimed that the 685-kb TCRB locus was the longest contiguous stretch of DNA analyzed to that time in humans.
Janeway et al. (2005) summarized the germline organization of the human TCR-beta locus. The TCR-beta locus contains a cluster of 52 functional V gene segments, each preceded by an exon encoding the leader sequence. The V gene cluster is followed by 2 separate clusters of genes. The first contains a D gene (TRBD1; 615447), 6 J genes, and a C gene (TRBC1), and the second contains a D gene (TRBD2; 615448), 7 J genes, and a C gene (TRBC2; 615445). Each C gene has separate exons encoding the constant domain, the hinge, the transmembrane region, and the cytoplasmic region.
The gene cluster for the beta subunit of T-cell antigen receptor is on chromosome 7 in man and on chromosome 6, near the immunoglobulin kappa light chain, in the mouse--an example of nonhomology of synteny (Caccia et al., 1984; Lee et al., 1984). Barker et al. (1984), using a cDNA probe in the study of mouse-human somatic cell hybrids, assigned the structural gene to chromosome 7. Collins et al. (1984) assigned the TCRB locus to the region 7q22-7qter. Prerequisite to beta-chain gene expression are rearrangements of variable (V), diversity (D), and joining (J) region elements into a transcriptional unit completed by the coding exons of the constant (C) region. Isobe et al. (1985) assigned the TCRB gene to 7q35 by in situ hybridization. They pointed out that this region is unusually prone to develop breaks in vivo and suggested that this may reflect instability generated by somatic rearrangement of T-cell receptor genes during normal differentiation in this cell lineage. Morton et al. (1985), also by in situ hybridization, put TCRB at or near 7q32. Related sequences were found on 7p15-7p21. The authors pointed to the chromosomal rearrangements that have been found at or near these sites in patients with ataxia-telangiectasia (208900) and other disorders. The possibility that the 7p localization found by Caccia et al. (1984) and by Morton et al. (1985) represents the site of TCRG (186970) is worthy of consideration. Ikuta et al. (1985) presented evidence that allelic exclusion occurs in the T-cell receptor gene, i.e., only 1 of the homologs is active.
Concannon et al. (1986) concluded that the repertoire of expressed human V(beta) genes is in excess of 59, apparently much smaller than the variable regions of the heavy and light chains. To ascertain the extent and organization of the germline human TCRB gene repertoire, Robinson et al. (1993) mapped beta-chain variable region genes by pulsed field gel electrophoresis, cosmid cloning, and in situ hybridization. Probes derived from the 24 known V families mapped to 6 SfiI fragments, 4 of which were linked to the TCRB gene complex on chromosome 7q35. The other 2 fragments, containing about 10% of the known V gene segments, were localized to a cluster of nonfunctional orphon gene segments located on chromosome 9. (Immunoglobulin V genes have also been found to be encoded outside of the immunoglobulin gene complexes (e.g., 147185) and have been designated orphon genes. This term combines the words orphan and exon.)
Gross (2013) mapped the TCR-beta locus, which contains the TRBC1 gene, to chromosome 7q34 based on an alignment of the TCR-beta locus sequence (GenBank L36092) with the genomic sequence (GRCh37).
Robinson and Kindt (1985) demonstrated RFLPs of the genes encoding the constant region of the T-cell antigen receptor. O'Connor et al. (1985) found rearrangement of the gene coding for the beta-chain of the T-cell receptor in all 6 T-cell leukemias and in 16 of 19 T-cell lymphomas; in all cases the immunoglobulin genes were in the germline arrangement. Contrariwise, all 36 B-cell leukemias and all 16 B-cell lymphomas showed rearranged immunoglobulin genes; the T-cell receptor genes were in germline configuration in all but 3.
Hockertz et al. (1998) studied the association of a gene linked to the TCRB variable region with cases of relapsing-progressive (RP) and relapsing-remitting (RR) multiple sclerosis (MS; 126200). They used a contingency-table test of patient data and affected family-based controls. Control alleles and haplotypes were composed of parental marker alleles and haplotypes not transmitted to the affected child in 90 simplex and 31 multiplex British Columbian families. In HLA class II DRw15(+) MS patients, the authors found that susceptibility to RP MS, but not RR MS, is associated with the recessive inheritance of a gene linked to the TCRB variable region. In DRw15(-) MS patients, they showed that susceptibility to the progressive form of the disease is associated with another gene linked to the TCRB variable region. They commented that the results of this study are supported by findings in 2 animal models of MS related to changes in the TCRB complex.
In Japanese families ascertained through asthmatic children, Noguchi et al. (1998) found evidence from affected sib-pair analyses for linkage between the TCRB gene on 7q35 and both specific IgE responses to the house dust mite and its purified allogens, high total serum IgE levels, and asthma. No evidence for linkage of IgE responses or asthma phenotype to the alpha-chain gene of TCR (TCRA; 186880) on 14q was found.
Aisenberg, A. C., Krontiris, T. G., Mak, T. W., Wilkes, B. M. Rearrangement of the gene for the beta chain of the T-cell receptor in T-cell chronic lymphocytic leukemia and related disorders. New Eng. J. Med. 313: 529-533, 1985. [PubMed: 2862584] [Full Text: https://doi.org/10.1056/NEJM198508293130901]
Barker, P. E., Ruddle, F. H., Royer, H. D., Reinherz, E. L. Chromosomal location of the beta chain gene of the human T-cell receptor complex. (Abstract) Am. J. Hum. Genet. 36: 132S only, 1984.
Bertness, V., Kirsch, I., Hollis, G., Johnson, B., Bunn, P. A., Jr. T-cell receptor gene rearrangements as clinical markers of human T-cell lymphomas. New Eng. J. Med. 313: 534-538, 1985. [PubMed: 3875035] [Full Text: https://doi.org/10.1056/NEJM198508293130902]
Born, W., Yague, J., Palmer, E., Kappler, J., Marrack, P. Rearrangement of T-cell receptor beta-chain genes during T-cell development. Proc. Nat. Acad. Sci. 82: 2925-2929, 1985. [PubMed: 3873070] [Full Text: https://doi.org/10.1073/pnas.82.9.2925]
Brennan, R. M., Petersen, J., Neller, M. A., Miles, J. J., Burrows, J. M., Smith, C., McCluskey, J., Khanna, R., Rossjohn, J., Burrows, S. R. The impact of a large and frequent deletion in the human TCR beta locus on antiviral immunity. J. Immun. 188: 2742-2748, 2012. [PubMed: 22323539] [Full Text: https://doi.org/10.4049/jimmunol.1102675]
Caccia, N., Kronenberg, M., Saxe, D., Haars, R., Bruns, G. A. P., Goverman, J., Malissen, M., Willard, H., Yoshikai, Y., Simon, M., Hood, L., Mak, T. W. The T cell receptor beta chain genes are located on chromosome 6 in mice and chromosome 7 in humans. Cell 37: 1091-1099, 1984. [PubMed: 6331676] [Full Text: https://doi.org/10.1016/0092-8674(84)90443-4]
Collins, M. K. L., Goodfellow, P. N., Dunne, M. J., Spurr, N. K., Solomon, E., Owen, M. J. A human T-cell antigen receptor beta chain gene maps to chromosome 7. EMBO J. 3: 2347-2349, 1984. [PubMed: 6548704] [Full Text: https://doi.org/10.1002/j.1460-2075.1984.tb02137.x]
Concannon, P., Pickering, L. A., Kung, P., Hood, L. Diversity and structure of human T-cell receptor beta-chain variable region genes. Proc. Nat. Acad. Sci. 83: 6598-6602, 1986. [PubMed: 3489234] [Full Text: https://doi.org/10.1073/pnas.83.17.6598]
Duby, A. D., Klein, K. A., Murre, C., Seidman, J. G. A novel mechanism of somatic rearrangement predicted by a human T-cell antigen receptor beta-chain complementary DNA. Science 228: 1204-1206, 1985. [PubMed: 3839095] [Full Text: https://doi.org/10.1126/science.3839095]
Gross, M. B. Personal Communication. Baltimore, Md. 9/30/2013.
Hedrick, S. M., Germain, R. N., Bevan, M. J., Dorf, M., Engel, I., Fink, P., Gascoigne, N., Heber-Katz, E., Kapp, J., Kaufmann, Y., Kaye, J., Melchers, F., Pierce, C., Schwartz, R. H., Sorensen, C., Taniguchi, M., Davis, M. M. Rearrangement and transcription of a T-cell receptor beta-chain gene in different T-cell subsets. Proc. Nat. Acad. Sci. 82: 531-535, 1985. [PubMed: 2578667] [Full Text: https://doi.org/10.1073/pnas.82.2.531]
Hockertz, M. K., Paty, D. W., Beall, S. S. Susceptibility to relapsing-progressive multiple sclerosis is associated with inheritance of genes linked to the variable region of the TcR beta locus: use of affected family-based controls. Am. J. Hum. Genet. 62: 373-385, 1998. [PubMed: 9463308] [Full Text: https://doi.org/10.1086/301700]
Ikuta, K., Ogura, T., Shimizu, A., Honjo, T. Low frequency of somatic mutation in beta-chain variable region genes of human T-cell receptors. Proc. Nat. Acad. Sci. 82: 7701-7705, 1985. [PubMed: 3865189] [Full Text: https://doi.org/10.1073/pnas.82.22.7701]
Isobe, M., Erikson, J., Emanuel, B. S., Nowell, P. C., Croce, C. M. Location of gene for beta subunit of human T-cell receptor at band 7q35, a region prone to rearrangement in T cells. Science 228: 580-582, 1985. [PubMed: 3983641] [Full Text: https://doi.org/10.1126/science.3983641]
Janeway, C. A., Jr., Travers, P., Walport, M., Shlomchik, M. J. Immunobiology: The Immune System in Health and Disease. (6th ed.). New York: Garland Science Publishing (pub.) 2005. Pp. 149-154, and 164-165.
Jones, N., Leiden, J., Dialynas, D., Fraser, J., Clabby, M., Kishimoto, T., Strominger, J. L., Andrews, D., Lane, W., Woody, J. Partial primary structure of the alpha and beta chains of human tumor T-cell receptors. Science 227: 311-314, 1985. [PubMed: 3871253] [Full Text: https://doi.org/10.1126/science.3871253]
Krell, P. F. I., Reuther, S., Fischer, U., Keller, T., Weber, S., Gombert, M., Schuster, F. R., Asang, C., Stepensky, P., Strahm, B., Meisel, R., Stoye, J., Borkhardt, A. Next-generation-sequencing-spectratyping reveals public T-cell receptor repertoires in pediatric very severe aplastic anemia and identifies a beta chain CDR3 sequence associated with hepatitis-induced pathogenesis. Haematologica 98: 1388-1396, 2013. [PubMed: 23716544] [Full Text: https://doi.org/10.3324/haematol.2012.069708]
Lee, K.-H., Holdorf, A. D., Dustin, M. L., Chan, A. C., Allen, P. M., Shaw, A. S. T cell receptor signaling precedes immunological synapse formation. Science 295: 1539-1542, 2002. [PubMed: 11859198] [Full Text: https://doi.org/10.1126/science.1067710]
Lee, N. E., D'Eustachio, P., Pravtcheva, D., Ruddle, F. H., Hedrick, S. M., Davis, M. M. Murine T cell receptor beta chain is encoded on chromosome 6. J. Exp. Med. 160: 905-913, 1984. [PubMed: 6206194] [Full Text: https://doi.org/10.1084/jem.160.3.905]
Maldonado, R. A., Irvine, D. J., Schreiber, R., Glimcher, L. H. A role for the immunological synapse in lineage commitment of CD4 lymphocytes. Nature 431: 527-532, 2004. [PubMed: 15386021] [Full Text: https://doi.org/10.1038/nature02916]
Malissen, M., McCoy, C., Blanc, D., Trucy, J., Devaux, C., Schmitt-Verhulst, A.-M., Fitch, F., Hood, L., Malissen, B. Direct evidence for chromosomal inversion during T-cell receptor beta-gene rearrangements. Nature 319: 28-33, 1986. [PubMed: 3484541] [Full Text: https://doi.org/10.1038/319028a0]
Morton, C. C., Duby, A. D., Eddy, R. L., Shows, T. B., Seidman, J. G. Genes for beta chain of human T-cell antigen receptor map to regions of chromosomal rearrangements in T cells. Science 228: 582-585, 1985. [PubMed: 3983642] [Full Text: https://doi.org/10.1126/science.3983642]
Noguchi, E., Shibasaki, M., Arinami, T., Takeda, K., Kobayashi, K., Matsui, A., Hamaguchi, H. Evidence for linkage between the development of asthma in childhood and the T-cell receptor beta chain gene in Japanese. Genomics 47: 121-124, 1998. [PubMed: 9465304] [Full Text: https://doi.org/10.1006/geno.1997.5054]
O'Connor, N. T. J., Wainscoat, J. S., Weatherall, D. J., Gatter, K. C., Feller, A. C., Isaacson, P., Jones, D., Lennert, K., Pallesen, G., Ramsey, A., Stein, H., Wright, D. H., Mason, D. Y. Rearrangement of the T-cell-receptor beta-chain gene in the diagnosis of lymphoproliferative disorders. Lancet 325: 1295-1297, 1985. Note: Originally Volume I. [PubMed: 2860492] [Full Text: https://doi.org/10.1016/s0140-6736(85)92791-6]
Patten, P., Yokota, T., Rothbard, J., Chien, Y.-H., Arai, K.-I., Davis, M. M. Structure, expression and divergence of T-cell receptor beta-chain variable regions. Nature 312: 40-46, 1984. [PubMed: 6092964] [Full Text: https://doi.org/10.1038/312040a0]
Pestano, G. A., Zhou, Y., Trimble, L. A., Daley, J., Weber, G. F., Cantor, H. Inactivation of misselected CD8 T cells by CD8 gene methylation and cell death. Science 284: 1187-1191, 1999. [PubMed: 10325233] [Full Text: https://doi.org/10.1126/science.284.5417.1187]
Robinson, M. A., Kindt, T. J. Segregation of polymorphic T-cell receptor genes in human families. Proc. Nat. Acad. Sci. 82: 3804-3808, 1985. [PubMed: 2987947] [Full Text: https://doi.org/10.1073/pnas.82.11.3804]
Robinson, M. A., Mitchell, M. P., Wei, S., Day, C. E., Zhao, T. M., Concannon, P. Organization of human T-cell receptor beta-chain genes: clusters of V-beta genes are present on chromosomes 7 and 9. Proc. Nat. Acad. Sci. 90: 2433-2437, 1993. [PubMed: 8384723] [Full Text: https://doi.org/10.1073/pnas.90.6.2433]
Rowen, L., Koop, B. F., Hood, L. The complete 685-kilobase DNA sequence of the human beta T cell receptor locus. Science 272: 1755-1762, 1996. [PubMed: 8650574] [Full Text: https://doi.org/10.1126/science.272.5269.1755]
Scott-Browne, J. P., White, J., Kappler, J. W., Gapin, L., Marrack, P. Germline-encoded amino acids in the alpha-beta T-cell receptor control thymic selection. Nature 458: 1043-1046, 2009. [PubMed: 19262510] [Full Text: https://doi.org/10.1038/nature07812]
Teixeiro, E., Daniels, M. A., Hamilton, S. E., Schrum, A. G., Bragado, R., Jameson, S. C., Palmer, E. Different T cell receptor signals determine CD8+ memory versus effector development. Science 323: 502-505, 2009. [PubMed: 19164748] [Full Text: https://doi.org/10.1126/science.1163612]
Tillinghast, J. P., Behlke, M. A., Loh, D. Y. Structure and diversity of the human T-cell receptor beta-chain variable region genes. Science 233: 879-883, 1986. [PubMed: 3755549] [Full Text: https://doi.org/10.1126/science.3755549]
Toyonaga, B., Yoshikai, Y., Vadasz, V., Chin, B., Mak, T. W. Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. Proc. Nat. Acad. Sci. 82: 8624-8628, 1985. [PubMed: 3866244] [Full Text: https://doi.org/10.1073/pnas.82.24.8624]
Trowbridge, I. S., Lesley, J., Trotter, J., Hyman, R. Thymocyte subpopulation enriched for progenitors with an unrearranged T-cell receptor beta-chain gene. Nature 315: 666-669, 1985. [PubMed: 3874369] [Full Text: https://doi.org/10.1038/315666a0]
Tunnacliffe, A., Kefford, R., Milstein, C., Forster, A., Rabbitts, T. H. Sequence and evolution of the human T-cell antigen receptor beta-chain genes. Proc. Nat. Acad. Sci. 82: 5068-5072, 1985. [PubMed: 3860845] [Full Text: https://doi.org/10.1073/pnas.82.15.5068]
van der Merwe, P. A., Davis, S. J. The immunological synapse--a multitasking system. Science 295: 1479-1480, 2002. [PubMed: 11859183] [Full Text: https://doi.org/10.1126/science.1069896]
Waldmann, T. A., Davis, M. M., Bongiovanni, K. F., Korsmeyer, S. J. Rearrangements of genes for the antigen receptor on T cells as markers of lineage and clonality in human lymphoid neoplasms. New Eng. J. Med. 313: 776-783, 1985. [PubMed: 2993886] [Full Text: https://doi.org/10.1056/NEJM198509263131303]
Weiss, L. M., Hu, E., Wood, G. S., Moulds, C., Cleary, M. L., Warnke, R., Sklar, J. Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy. New Eng. J. Med. 313: 539-544, 1985. [PubMed: 4022090] [Full Text: https://doi.org/10.1056/NEJM198508293130903]