Excerpt from Annual Report of Intramural Activities: October 1, 1986-September 30, 1987
Within the last year we have synthesized over 300 peptides for use in 50 separate studies. In collaboration with David Margulies’s lab (li), antipeptide sera reactive with the C-terminus of murine major histocompatibility complex class I molecules have been used to investigate alternative rna splicing patterns in various mouse strains and cell types. In collaboration with the laboratories of John Coligan (brb), Ron Schwartz (li) and Ethan Schevach (li) antipeptide sera hav been used to identify a second T cell receptor for antigen in the mouse. We have followed the ontogeny of the new receptor, investigate the assembly of the recepto complex and identified which subsets of T cells express the receptor. The assembl of the primary T cell receptor complex on human T cells has been studied with antipeptides sera which are specific for the individual proteins of the complex. In work done in collaboration with Louis Miller’s Lab (lpd), synthetic peptides have been used extensively to study the malaria parasite and the immune response i generates. Three histidine rich proteins present in the infected erythrocyte have been characterized. We have also defined the immunodominate epitope on the circumsporozoite protein; in both human and rodent malarias. In addition to the definition of B cell epitopes on the circumsporozoite protein we have also used synthetic peptides to define T cell epitopes in the human malaria Plasmodium falciparum. By conjugating the immunodominate B cell epitope with the major T cell epitope we have constructed a synthetic immunogen capable of generating an antisporozoite response in mice unresponsive to either peptide separately. In collaboration with Ron Schwartz’s lab we have defined a helper T cell epitope in the cytochrome C molecule. Using this knowledge we have made a set of synthetic peptides where the proposed T cell receptor contact amino acids are changed. Each member of this set produced a specific T cell response when injected in mice, indicating that there are no holes in the T cell response to this epitope.
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