A human minor histocompatibility antigen which appears to segregate with the major histocompatibility complex.

ABSTRACT

We obtained a cell line (So1) from a patient who rejected a T-depleted allogeneic BMT. Cytotoxic activity by cell-mediated lympholysis was found using So1 as effector and EBV-transformed donor B cells as targets, but no lysis of the patient's pretransplantation cells and of an unrelated HLA-nonidentical subject was observed, suggesting it was related to recognition of a minor transplantation antigen which could have contributed to rejection of the graft. To define the HLA-restricting element(s), cell-mediated lympholysis experiments were performed with several B cell lines as targets. So1 lysed only targets sharing an HLA-B44 antigen with the patient, thus demonstrating that the minor transplantation antigen recognized was restricted by HLA-B44. The absence of lysis against the patient's pretransplantation cells may be related to the absence of the minor antigen, suggesting that the patient's cytotoxic lymphocytes able to recognize a minor transplantation antigen on the donor cells contributed to the rejection of the HLA-identical graft. Mendelian segregation of this minor antigen was found in familial studies. Lysis was observed with cells from members of 2 families who had an association of HLA-B44 antigen in the haplotype and the minor antigen, whereas in 2 other HLA-B44-positive families, no lysis was found, probably because this minor antigen was absent. Furthermore, these family studies (1) demonstrated that this minor antigen segregates with the MHC, suggesting its localization on chromosome 6; and (2) showed a close relationship between the minor antigen and HLA-B44, strongly suggesting a linkage disequilibrium between the minor antigen and its restriction antigen B44.