Gene mapping and somatic cell hybrid analysis of the role of human lymphocyte function-associated antigen-3 (LFA-3) in CTL-target cell interactions.
LFA-3 is expressed on a wide variety of human cell lines, including those which have been used as recipients for gene transfer of human class I gene products, whereas a murine counterpart is either absent or significantly different such that the anti-LFA-3 monoclonal antibody (MAb) does not bind. By using a somatic cell genetic approach, we demonstrate that LFA-3 is not a major histocompatibility complex-encoded molecule, and that its gene locus maps to human chromosome 1. When LFA-3 and HLA-A2 are coexpressed on the mouse cell surface, anti-LFA-3 MAb interfered with specific recognition and lysis of these target cells by human CTL capable of lysing HLA-A2-expressing mouse transfectants. A significant contribution of the LFA-3 molecule to CTL reactivity was not observed, however, because the presence of LFA-3 did not restore recognition by CTL clones previously found incapable of lysing HLA-A2-expressing mouse transfectants, nor was it required by those human CTL that could lyse mouse cell transfectants. Thus, we have used genetic techniques to demonstrate that LFA-3 may serve a role in CTL-target cell interactions at the target cell level, but is not a molecule absolutely required for human allospecific CTL recognition of HLA antigens expressed on mouse cells. We suggest that LFA-3 may not participate directly in CTL function under normal circumstances, but delivers a more general inhibitory signal only when provoked by bound MAb.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D001029:Aotus trivirgatus; D002450:Cell Communication; D002460:Cell Line; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics; D015789:HLA-A2 Antigen; D006801:Humans; D006822:Hybrid Cells / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000954:Antigens, Surface; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D016169:Lymphocyte Function-Associated Antigen-1