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T cells specific for different antigens express different HLA-D region products
Abstract:
T cell lines and clones were analyzed for surface expression of Ia antigens using monoclonal antibodies (mAb) that detect monomorphic and polymorphic epitopes on Ia molecules encoded by the HLA-DR and HLA-DQ gene clusters. All mAb bound to B lymphocytes or lymphoblastoid cell lines of the same individuals from whom the T cells were derived. Three mAb detecting monomorphic epitopes, primarily associated with HLA-DR, bound to all T cells showing that each clone or line expressed some type of Ia. Three other mAb defining polymorphic epitopes associated with HLA-DR products showed differential binding patterns. Two reagents, R3 and E15/4 recognizing the supertypic specificity DRw52 (formerly MT2), bound to every alloreactive clone, whereas the 16.23 mAb, detecting a private DR3-associated epitope, failed to bind to any clone. In contrast, the 16.23 epitope was detected on high percentages of T cells specific for purified protein derivative of tuberculin (PPD) or tetanus toxoid (TT). Biochemical studies showed that the 16.23 and DRw52-like epitopes can be present on distinct DR molecules on B cell lines and this may also be the case for T cells. Three other mAb, detecting epitopes associated with HLA-DQ, also revealed differential binding patterns when tested on various T cells. Two failed to bind to any alloreactive clone and to only low numbers of PPD- or TT-specific T cell lines, whereas the third bound distinctly to a CD4+/CD8+ alloreactive clone. Biochemical analyses have shown that these DQ epitopes can be present on different molecules. Combined, these observations indicate that differential expression of Ia molecules encoded by both HLA-DR and DQ occurs between B and activated T cells as well as among T cell populations of the same individual. Whether these differences reflect quantitative variations in expression of given DR or DQ molecules or, alternatively, are due to differential class II gene expression in activated T cells remains to be determined.