TY  - JOUR
AU  - Zernich, D
AU  - Purcell, AW
AU  - Macdonald, WA
AU  - Kjer-Nielsen, L
AU  - Ely, LK
AU  - Laham, N
AU  - Crockford, T
AU  - Mifsud, NA
AU  - Bharadwaj, M
AU  - Chang, L
AU  - Tait, BD
AU  - Holdsworth, R
AU  - Brooks, AG
AU  - Bottomley, SP
AU  - Beddoe, T
AU  - Peh, CA
AU  - Rossjohn, J
AU  - McCluskey, J
Y2  - 2014/05/21
Y1  - 2004/07/05
SN  - 0022-1007
UR  - http://hdl.handle.net/11343/26153
AB  - 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.
N1  - application/pdf
LA  - English
PB  - ROCKEFELLER UNIV PRESS
KW  - Immunogenetics ; Infectious Diseases; Immune System and Allergy
T1  - Natural HLA class 1 polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion
DO  - 10.1084/jem.20031680
IS  - JOURNAL OF EXPERIMENTAL MEDICINE
VL  - 200
IS  - 1
SP  - 13-24
L1  - /bitstream/handle/11343/26153/115916_4958.pdf?sequence=1&isAllowed=n
ER  -