The biochemistry and cell biology of antigen presentation by MHC class I and class II molecules. Implications for development of combination vaccines.
T lymphocytes play a central role in adaptive immunity. They provide direct effector function, regulate the activity of non-antigen-specific effector cells such as macrophages, and control the production of antibodies by B cells. Thus, the proper stimulation of T cells is critical to effective vaccination. T cells bearing alpha beta receptors are stimulated by antigen-derived peptides displayed on cell surfaces bound to highly polymorphic, major histocompatibility complex-encoded glycoproteins. To elicit suitable T cell responses vaccines must, therefore, contain proteins or peptides derived from the organism against which protection is desired, the pathogen-derived peptides must be capable of interacting with the allelic forms of the MHC molecules expressed in the vaccinated individuals, and the vaccine components must be delivered in a manner that ensures they are made available for binding to the MHC molecules on appropriate antigen-presenting cells. This paper has reviewed the rules governing peptide binding to MHC molecules, the intracellular pathways of protein synthesis, protein degradation, and protein and peptide transport involved in bringing together antigenic peptides and MHC molecules, and the distinct function of MHC class I versus class II molecules. The implications of this knowledge for effective combined vaccine design and delivery were considered.
Germain
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RN
Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001665:Binding Sites; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D017778:Vaccines, Combined / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D017778:Vaccines, Combined