EVIDENCE FOR STRUCTURAL HOMOLOGY BETWEEN MURINE AND HUMAN IA ANTIGENS

The serological cross-reactivity and the structural homology of murine and human Ia alloantigens were analyzed. Normal human peripheral blood B [bone marrow-derived] lymphocytes and chronic lymphocytic leukemia (CLL) cells were lysed in the presence of complement by murine anti-Ia and human anti-HLA-DR alloantisera. A mouse A.TH anti-A.TL (anti-Ik) alloantiserum reacted with determinants expressed on all 20 normal human B cell populations tested. Only 3 of these 20 B cell populations were lysed with an A.TL anti-A.TH anti-Is alloantiserum. The frequency of cytotoxic cross-reactivity concordant with anti-Ik appears to be greater for anti-I-ECk than for anti-I-Ak alloreactivity. Immunochemical analysis demonstrated that Ia .alpha.-chain and .beta.-chain polypeptides may be immunoprecipitated from CLL cell lysates by a mouse anti-Ik alloantiserum or various human anti-HLA-DR alloantisera. The Ia molecules detected with the mouse and human antisera are coprecipitable as revealed by 1-dimensional gel electrophoresis. Two-dimensional gel electrophoresis studies indicated that the human CLL cell Ia antigens analyzed possess considerable molecular heterogeneity. They are structurally more similar, with respect to molecular size and charge, to mouse Ia antigens determined by the murine H-2-linked I-EC subregion rather than the I-A subregion. The structural, genetic and functional implications of these findings were discussed.