EPITOPE ANALYSIS OF THE T-CELL RESPONSE TO A COMPLEX ANTIGEN - PROLIFERATIVE RESPONSES TO HUMAN RHINOVIRUS CAPSIDS

Understanding the factors which regulate the repertoire of a T cell re sponse is important when selecting T helper cell epitopes for inclusio n in synthetic viral vaccines. In this study we have examined the T ce ll response to human rhinovirus (HRV) type 1 A in a mouse model system , using a comprehensive set of synthetic peptides which span all four ot the proteins which make up the HRV capsid. This constitutes the fir st study to use a set of peptides covering the entire sequence of all structural proteins of any virus. This study identifies the major prol iferative (CD4) T cell epitopes within the minor receptor group HRV 1 A, and analyzes these epitopes with relation to their location within the three-dimensional structure of the virus. The proliferative respon se to HRV is highly selective, with strong responses to only a very sm all number of epitopes, many of which are grouped together within rest ricted areas of the primary structure of the HRV proteins. The reperto ire of the response is almost entirely specific to the major histocomp atibility complex haplotype of the host. The major T cell epitopes are spatially distinct from the sites of the major antibody recognition s ites, and are buried within the viral capsid. In striking contrast to the antibody responses, the T cell responses are highly cross-reactive against a wide variety of viral serotypes.