HUMAN HELPER T-CELL CLONES THAT RECOGNIZE DIFFERENT INFLUENZA HEMAGGLUTININ DETERMINANTS ARE RESTRICTED BY DIFFERENT HLA-D REGION EPITOPES

Human T-lympohcyte clones (TLC) were generated against the hemagglutinin (HA) of A/Texas/1/77 influenza virus by limiting dilution. TLC were then screened for antigen specificity on chemically synthesized peptides representing the HA1 molecule. Hypothetically, different T cells that recognize the identical antigenic determinants are controlled by (restricted by) the same class II epitope. Two TLC, HA1.4 and HA1.7, both recognized the same HA peptide and in proliferation studies exhibited identical restriction patterns. Two other clones, HA 1.9 and HA 2.43, recognized different HA determinants and also had distinct restriction patterns. Proliferation inhibition studies with monoclonal antibodies against human class II moelcules demonstrated 3 unique patterns of blocking with the clones, suggesting that clones may be restricted to a unique class II epitope depending on the HA determinant recognized. These data can be interpreted as supporting the argument that human immune responses to influenza hemagglutinin are under Ir gene control exerted at the level of the viral antigenic determinant recognized in association with particular D-region restricting elements. The determinant selection and clonal deletion theories are compared for their capacity to best explain these findings.