PMID: 2479631Jan 1, 1988Paper

Mechanisms of immunodominance in T-cell recognition, with applications to vaccine design.

Princess Takamatsu Symposia
J A Berzofsky

Abstract

Immunodominant T-cell antigenic sites can so dominate a response that their presence leads to high responsiveness and their absence to low responsiveness. Therefore, it is important to locate such sites for vaccine development. Factors that lead to immunodominance include features extrinsic to the structure of the site itself, such as the major histocompatibility complex (MHC) molecules of the host and the types of fragments produced by processing of the protein antigen before the T cell sees it. They also include factors intrinsic to the structure of the T-cell site, that determine a repertoire of potential immunodominant sites from which the extrinsic factors select a subset that will be immunodominant in a given individual. We have focused on one of these intrinsic factors, helical amphipathicity, that we have found to be a common feature among both helper and cytotoxic T-cell antigenic sites, suggesting that the same physical principles apply to sites seen in association with class I and class II MHC molecules. We have used this feature to locate immunodominant epitopes on the circumsporozoite protein of the Plasmodium falciparum malaria parasite and the envelope protein of the AIDS virus. Both helper and cytotoxic T-cell e...Continue Reading

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