HLA class II-like antiidiotypic antibodies from highly sensitized patients inhibit T-cell alloresponses.
The purpose of this study is to identify factors in the sera of highly sensitized (HS) patients (pts) that inhibit T-cell alloresponses. An in vitro assay was used to measure HLA class I and class II-like antiidiotypic antibodies (anti-ids). The stimulation index (SI) was used to measure PBL and T-cell responses to alloantigens. All HS sera (32 pts) and the IgG fraction inhibited PBL and CD4(+) T-cell responses to alloantigens. The SI with HS IgG was 7.9 +/- 1.7 as compared to 31.5 +/- 5.9 with normal IgG (p = 0.0003). In a subset of pts who were transiently sensitized, the SI was 6.6 +/- 1.0 with a high panel reactive antibody (PRA), but when their PRA was zero, the SI was 17.8 +/- 1.3 (p = 0.0000001). Anti-ids were found in 100% of 17 pts with a high PRA. The T-cell inhibitory factors reduced CD4(+) T-cell responses of HS pts to alloantigens in the presence of autologous anti-ids, were MHC restricted and were inactivated by in vitro generated antibodies to HLA class II-like anti-ids. The HLA class II-like anti-id IgG molecules bind to the TCR of CD4(+) T cells and may impair their ability to help in the downregulating antibody response to anti-ids.
Hack
N
N
Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.
Angra
S
S
McKnight
T
T
Denhollander
N
N
Cardella
C J
CJ
D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000502:physiology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D007106:Immune Sera; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes