It is established that T cells recognize antigens as processed fragments (peptides) bound to MHC molecules. The immunologically relevant peptides appear to be a limited number for every protein antigen. Such """"""""immunodominant"""""""" sites have been characterized for different viral proteins. For HIV (human immunodeficiency virus) this identification has been hampered by the generally immunosuppressed state of the infected individuals. Our proposal is to circumvent this problem with the direct study of the binding of the H.I.V. peptides to Class II MHC. This will be done using as binding molecules Class II MHC of a panel of viable MHC homozygous human B cell lines. Both direct binding of radiolabelled H.I.V. peptides and the inhibition by unlabeled H.I.V. peptides of the binding of a labeled influenza matrix peptide will be studied. The reasons for studying the binding to MHC on a panel of viable cells are twofold: first we shall be able to study the interaction of a large number of peptides with a variety of Class II MHC types in a reasonable amount of time, and second we shall approach the condition in real life where ready made peptides (if included in a vaccine) will be presented to CD4+ T cells largely by Class II MHC on the membrane of B cells. Therefore, our work should be relevant not only for studies aiming at the definition of the immune status of H.I.V. infected individuals, but also for the design of vaccines that include synthetic H.I.V. peptides.

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National Institute of Allergy and Infectious Diseases (NIAID)
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Columbia University (N.Y.)
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