T cell recognition of allopeptides in context of syngeneic MHC.
We have analyzed the ability of T cells to recognize peptides corresponding in sequence to an allogeneic HLA-DR molecule, in context of syngeneic MHC. PBMC from a responder with the HLA-DR beta 1*1101/DR beta 1*1201 genotype were stimulated in vitro with a mixture of four synthetic peptides derived from the first domain of the DR beta 1*0101 chain (amino acid residue 1-20, 21-42, 43-62, and 66-90). An alloreactive T cell line, TCL-LS, which proliferates only in response to peptide 21-42 presented by HLA-DR beta 1*1101, was obtained. The blastogenic response of the line was inhibited by anti-HLA-DR and CD4 antibodies but was not affected by antibodies to HLA-DQ, HLA-DP, HLA-ABC, and CD8. In the presence of irradiated, autologous APC, TCL-LS displayed specific proliferative responses to stimulating cells obtained from individuals carrying the DR beta 1*0101 allele. In the absence of autologous APC, TCL-LS recognized HLA-DR1 on allogeneic cells only when expressed together with HLA-DR beta 1*1101, the restrictive element. This indicates that TCL-LS recognizes processed HLA-DR1 molecule presented as nominal Ag. Study of TCR-V beta gene repertoire expressed by TCL-LS showed that only two V beta genes were used (V beta 13.2 and V beta 12). Two T cell clones (TCC) derived from this line, TCC-A5 and B4, exhibited a similar pattern of reactivity and expressed V beta 13.2. These results indicate that T cells recognizing peptides, which are derived from the breakdown of allogeneic MHC class II proteins and are presented by self-HLA-DR molecules, participate in allorecognition.
Liu
Z
Z
College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Braunstein
N S
NS
Suciu-Foca
N
N
D000938:Antigen-Presenting Cells / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002460:Cell Line; D015870:Gene Expression; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008285:Major Histocompatibility Complex; D010455:Peptides / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D001324:Autoantigens; D015798:HLA-DR1 Antigen; D010455:Peptides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta