The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families.
To define the phenotype and T cell receptor (TCR) repertoire of CD1d-dependent T cells, we compared the populations of T cells that persisted in major histocompatibility complex (MHC)-deficient mice, which lack mainstream T cells, with those from MHC/CD1d doubly deficient mice, which lack both mainstream and CD1d-dependent T cells. Surprisingly, up to 80% of the CD1d-dependent T cells were stained by tetramers of CD1d/alpha-galactosylceramide, which specifically identify the previously described CD1d autoreactive Valpha14-Jalpha18/Vbeta8 natural killer (NK) T cells. Furthermore, zooming in on the CD1d-dependent non-Valpha14 T cells, we found that, like Valpha14 NK T cells, they mainly expressed recurrent, CD1d autoreactive TCR families and had a natural memory phenotype. Thus, CD1d-restricted T cells differ profoundly from MHC-peptide-specific T cells by their predominant use of autoreactive and semiinvariant, rather than naive and diverse, TCRs. They more closely resemble other lineages of innate lymphocytes such as B-1 B cells, gammadelta T cells, and NK cells, which express invariant or semiinvariant autoreactive receptors. Finally, we demonstrate that the MHC-restricted TCR repertoire is essentially non-cross-reactive to CD1d. Altogether, these findings imply that lipid recognition by CD1d-restricted T cells may have largely evolved as an innate rather than an adaptive arm of the mouse immune system.
Park
S H
SH
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA. sehopark@korea.ac.kr
Weiss
A
A
Benlagha
K
K
Kyin
T
T
Teyton
L
L
Bendelac
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta