Diverse TCRs recognize murine CD1.
Human and murine T cells that specifically recognize CD1d and produce IL-4 and IFN-gamma play a role in immunoregulation and tumor rejection. In the mouse, most CD1d1-reactive T cells described express an invariant Valpha14-Jalpha281 TCR associated with TCR beta-chains of limited diversity. Similarly, human CD1d-reactive T cells express a highly restricted TCR repertoire. Here we report the unexpected result that in mice immunized with CD1d1-bearing transfectant cells, a diverse repertoire of TCRs was expressed by CD1d1-reactive T cell clones isolated by limiting dilution without preselection for NK1 expression. Only 3 of 10 CD1d1-reactive T cell clones expressed the invariant Valpha14-Jalpha281 TCRalpha rearrangement. T cells expressing Valpha10, -11, -15, and -17, and having non-germline-encoded nucleotides resulting in diverse V-J junctions were identified. Like CD1d1-reactive T cells expressing the invariant Valpha14-Jalpha281 TCR alpha-chain, CD1d1-reactive clones with diverse TCRs produced both Type 1 (IFN-y) and Type 2 (IL-4, IL-10) cytokines. This establishes the existence of significant diversity in the TCRs directly reactive to the CD1d1 protein. Our findings reveal that CD1d interacts with a broad array of TCRs, suggesting substantial redundancy and flexibility of the immune system in providing T cells serving the role(s) mediated by CD1d reactivity.
Behar
S M
SM
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Podrebarac
T A
TA
Roy
C J
CJ
Wang
C R
CR
Brenner
M B
MB
D000595:Amino Acid Sequence; D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000276:immunology; D016399:Lymphoma, T-Cell; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018949:Antigens, CD1; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell