HLA RESTRICTION OF HUMAN CYTOTOXIC T LYMPHOCYTES SPECIFIC FOR INFLUENZA VIRUS Poor Recognition of Virus Associated with HLA A2 By ANDREW McMICHAEL*

Cytotoxic T lymphocytes that are specific for virus antigen expressed at the surface of infected cells, have been demonstrated in mice infected with several viruses (1-6) . We have recently described the induction of such cells from human peripheral blood lymphocytes (7) . t Murine Cytotoxic T cells show specificity for both the viral and H-2 antigens on the infected target cell (1-6) . Killer and target cells must share H-2 antigens of the K and D series (1-6) . la antigens do not influence this interaction though Schmidt-Verhulst and Shearer (8) and Gordon and Simpson (9) have shown that I region products can influence the generation of Cytotoxic T cells in vitro . The requirement for H-2 sharing (H-2 restriction) has been shown for several viruses including lymphocytec chorio meningitis virus, vaccinia, ectromelia, influenza, and Friend leukemia virus (1-6) . These findings suggest that the natural function of H-2 antigens might be to interact with viruses in the immune response to virus infection . The H-2 restriction phenomenon, however, is not limited to virus infection ; it is also seen for Cytotoxic cells generated against chemically altered cell surface products (8) or to minor transplantation antigens (9, 10) . Demonstration of HLA restriction of human Cytotoxic cell activity has been more difficult, probably because of technical and ethical problems in experimental design . However, HLA restriction has been demonstrated for Cytotoxic T-cell lysis of cells differing in minor transplantation antigens (11), of cells that have been dinitrophenylated (12) and of cells infected with influenza viruses (7) . This report extends the evidence for HLA antigen restriction in cytotoxicity of influenza virus infected cells. The A and B loci are shown to be involved and it is demonstrated that there is a deficiency in Cytotoxic T lymphocyte recognition of influenza virus associated with HLA A2.