An Invariant T Cell Receptor Alpha Chain is Used by a Unique Subset of Major Histocompatibility Complex Class I-specific CD4+ and CD4-8- T Cells in Mice and Humans

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1994 Sep 1

PMID 7520467

Citations 415

Authors

O Lantz

A Bendelac

Affiliations

Soon will be listed here.

Abstract

The mouse thymus contains a mature T cell subset that is distinguishable from the mainstream thymocytes by several characteristics. It is restricted in its usage of T cell receptor (TCR) V beta genes to V beta 8, V beta 7, and V beta 2. Its surface phenotype is that of activated/memory cells. It carries the natural killer NK1.1 surface marker. Furthermore, though it consists entirely of CD4+ and CD4-8- cells, its selection in the thymus depends solely upon major histocompatibility complex (MHC) class I expression by cells of hematopoietic origin. Forced persistence of CD8, in fact, imparts negative selection. Here, we have studied the TCR repertoire of this subset and found that, whereas the beta chain V-D-J junctions are quite variable, a single invariant alpha chain V alpha 14-J281 is used by a majority of the TCRs. This surprisingly restricted usage of the V alpha 14-J281 alpha chain is dependent on MHC class I expression, but independent of the MHC haplotype. In humans, a similar unusual population including CD4-8- cells can also be found that uses a strikingly homologous, invariant alpha chain V alpha 24-JQ. Thus, this unique V alpha-J alpha combination has been conserved in both species, conferring specificity to some shared nonpolymorphic MHC class I/peptide self-ligand(s). This implies that the T cell subset that it defines has a specialized and important role, perhaps related to its unique ability to secrete a large set of lymphokines including interleukin 4, upon primary stimulation in vitro and in vivo.

Citing Articles

T Cell Development: From T-Lineage Specification to Intrathymic Maturation.

Golzari-Sorkheh M, Yoganathan K, Chen E, Singh J, Zuniga-Pflucker J Adv Exp Med Biol. 2025; 1471:81-137.

PMID: 40067585 DOI: 10.1007/978-3-031-77921-3_4.

The T cell receptor sequence influences the likelihood of T cell memory formation.

Lagattuta K, Kohlgruber A, Abdelfattah N, Nathan A, Rumker L, Birnbaum M Cell Rep. 2024; 44(1):115098.

PMID: 39731734 PMC: 11785489. DOI: 10.1016/j.celrep.2024.115098.

Identification of α-galactosylceramide as an endogenous mammalian antigen for iNKT cells.

Hosono Y, Tomiyasu N, Kasai H, Ishikawa E, Takahashi M, Imamura A J Exp Med. 2024; 222(2).

PMID: 39704712 PMC: 11660903. DOI: 10.1084/jem.20240728.

Identification of Functional Immune Biomarkers in Breast Cancer Patients.

Derakhshandeh R, Zhu Y, Li J, Hester D, Younis R, Koka R Int J Mol Sci. 2024; 25(22).

PMID: 39596374 PMC: 11595306. DOI: 10.3390/ijms252212309.

Lipid accumulation in adipose tissue-resident iNKT cells contributes to an inflammatory phenotype.

Morris I, Vrieling F, Bouwman A, Stienstra R, Kalkhoven E Adipocyte. 2024; 13(1):2421750.

PMID: 39484712 PMC: 11540091. DOI: 10.1080/21623945.2024.2421750.

References

Altschul S, Gish W, Miller W, Myers E, Lipman D . Basic local alignment search tool. J Mol Biol. 1990; 215(3):403-10. DOI: 10.1016/S0022-2836(05)80360-2. View

Arase H, Arase N, Ogasawara K, GOOD R, Onoe K . An NK1.1+ CD4+8- single-positive thymocyte subpopulation that expresses a highly skewed T-cell antigen receptor V beta family. Proc Natl Acad Sci U S A. 1992; 89(14):6506-10. PMC: 49530. DOI: 10.1073/pnas.89.14.6506. View

HERSHBERG R, Eghtesady P, Sydora B, Brorson K, Cheroutre H, Modlin R . Expression of the thymus leukemia antigen in mouse intestinal epithelium. Proc Natl Acad Sci U S A. 1990; 87(24):9727-31. PMC: 55246. DOI: 10.1073/pnas.87.24.9727. View

Koseki H, Asano H, Inaba T, Miyashita N, Moriwaki K, Lindahl K . Dominant expression of a distinctive V14+ T-cell antigen receptor alpha chain in mice. Proc Natl Acad Sci U S A. 1991; 88(17):7518-22. PMC: 52332. DOI: 10.1073/pnas.88.17.7518. View

Grusby M, Johnson R, Papaioannou V, Glimcher L . Depletion of CD4+ T cells in major histocompatibility complex class II-deficient mice. Science. 1991; 253(5026):1417-20. DOI: 10.1126/science.1910207. View

Takahama Y, Sharrow S, Singer A . Expression of an unusual T cell receptor (TCR)-V beta repertoire by Ly-6C+ subpopulations of CD4+ and/or CD8+ thymocytes. Evidence for a developmental relationship between Ly-6C+ thymocytes and CD4-CD8-TCR-alpha beta+ thymocytes. J Immunol. 1991; 147(9):2883-91. View

Rotzschke O, Falk K, Faath S, Rammensee H . On the nature of peptides involved in T cell alloreactivity. J Exp Med. 1991; 174(5):1059-71. PMC: 2118982. DOI: 10.1084/jem.174.5.1059. View

Imani F, Soloski M . Heat shock proteins can regulate expression of the Tla region-encoded class Ib molecule Qa-1. Proc Natl Acad Sci U S A. 1991; 88(23):10475-9. PMC: 52951. DOI: 10.1073/pnas.88.23.10475. View

Casanova J, Romero P, Widmann C, Kourilsky P, Maryanski J . T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire. J Exp Med. 1991; 174(6):1371-83. PMC: 2119045. DOI: 10.1084/jem.174.6.1371. View

10.

Bendelac A, Matzinger P, Seder R, Paul W, Schwartz R . Activation events during thymic selection. J Exp Med. 1992; 175(3):731-42. PMC: 2119155. DOI: 10.1084/jem.175.3.731. View

11.

Boitel B, Ermonval M, Panina-Bordignon P, Mariuzza R, Lanzavecchia A, Acuto O . Preferential V beta gene usage and lack of junctional sequence conservation among human T cell receptors specific for a tetanus toxin-derived peptide: evidence for a dominant role of a germline-encoded V region in antigen/major histocompatibility.... J Exp Med. 1992; 175(3):765-77. PMC: 2119152. DOI: 10.1084/jem.175.3.765. View

12.

OBRIEN R, Fu Y, Cranfill R, Dallas A, Ellis C, Reardon C . Heat shock protein Hsp60-reactive gamma delta cells: a large, diversified T-lymphocyte subset with highly focused specificity. Proc Natl Acad Sci U S A. 1992; 89(10):4348-52. PMC: 49079. DOI: 10.1073/pnas.89.10.4348. View

13.

Hayakawa K, Lin B, Hardy R . Murine thymic CD4+ T cell subsets: a subset (Thy0) that secretes diverse cytokines and overexpresses the V beta 8 T cell receptor gene family. J Exp Med. 1992; 176(1):269-74. PMC: 2119274. DOI: 10.1084/jem.176.1.269. View

14.

Malissen M, Trucy J, Jouvin-Marche E, Cazenave P, Scollay R, Malissen B . Regulation of TCR alpha and beta gene allelic exclusion during T-cell development. Immunol Today. 1992; 13(8):315-22. DOI: 10.1016/0167-5699(92)90044-8. View

15.

Itohara S, Mombaerts P, Lafaille J, Iacomini J, Nelson A, Clarke A . T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes. Cell. 1993; 72(3):337-48. DOI: 10.1016/0092-8674(93)90112-4. View

16.

Asarnow D, Cado D, Raulet D . Selection is not required to produce invariant T-cell receptor gamma-gene junctional sequences. Nature. 1993; 362(6416):158-60. DOI: 10.1038/362158a0. View

17.

Reiner S, Wang Z, Hatam F, Scott P, Locksley R . TH1 and TH2 cell antigen receptors in experimental leishmaniasis. Science. 1993; 259(5100):1457-60. DOI: 10.1126/science.8451641. View

18.

Chan S, Cosgrove D, Waltzinger C, Benoist C, Mathis D . Another view of the selective model of thymocyte selection. Cell. 1993; 73(2):225-36. DOI: 10.1016/0092-8674(93)90225-f. View

19.

Makino Y, Yamagata N, Sasho T, Adachi Y, Kanno R, Koseki H . Extrathymic development of V alpha 14-positive T cells. J Exp Med. 1993; 177(5):1399-408. PMC: 2191006. DOI: 10.1084/jem.177.5.1399. View

20.

Dellabona P, Casorati G, Friedli B, Angman L, Sallusto F, Tunnacliffe A . In vivo persistence of expanded clones specific for bacterial antigens within the human T cell receptor alpha/beta CD4-8- subset. J Exp Med. 1993; 177(6):1763-71. PMC: 2191040. DOI: 10.1084/jem.177.6.1763. View