Natural HLA class 1 polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion
AuthorZernich, D; Purcell, AW; Macdonald, WA; Kjer-Nielsen, L; Ely, LK; Laham, N; Crockford, T; Mifsud, NA; Bharadwaj, M; Chang, L; ...
Source TitleJOURNAL OF EXPERIMENTAL MEDICINE
PublisherROCKEFELLER UNIV PRESS
University of Melbourne Author/sPURCELL, ANTHONY; Kjer-Nielsen, Lars; Bharadwaj, Mandvi; Tait, Brian; Brooks, Andrew; McCluskey, James; CHANG, LINUS; MIFSUD, NICOLE; BURNS, DANIELLE; MACDONALD, WHITNEY ALISON; ...
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsZernich, D., Purcell, A. W., Macdonald, W. A., Kjer-Nielsen, L., Ely, L. K., Laham, N., Crockford, T., Mifsud, N. A., Bharadwaj, M., Chang, L., Tait, B. D., Holdsworth, R., Brooks, A. G., Bottomley, S. P., Beddoe, T., Peh, C. A., Rossjohn, J. & McCluskey, J. (2004). Natural HLA class 1 polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion. JOURNAL OF EXPERIMENTAL MEDICINE, 200 (1), pp.13-24. https://doi.org/10.1084/jem.20031680.
Access StatusAccess this item via the Open Access location
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213310
C1 - Journal Articles Refereed
HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.
KeywordsImmunogenetics ; Infectious Diseases; Immune System and Allergy
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