The impact of HLA-class I and EBV-latency-II antigen-specific XXXX (+) T-cells on the pathogenesis of EBV(+) @entity978 .

@entity1 @entity1529 @entity25062 @entity978 @entity405
UNASSIGNED: In 40% of cases of classical @entity978 (cHL), EBV-latency-II antigens (EBNA1/ @entity25062 /LMP2A) are present (EBV(+) cHL) in the malignant cells and antigen presentation is intact. Previous studies have consistently shown that @entity1529 *02 is protective in EBV(+) cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, @entity405 and LMP2A expression were strongly correlated and, for a given LMP2A level, @entity405 was markedly elevated in @entity1529 *02(-ve) versus @entity1529 *02(+) EBV(+) cHL @entity1 , suggesting that LMP2A-specific @entity405 (+) T-cell anti-tumoral immunity may be relatively ineffective in @entity1529 *02(-ve) EBV(+) cHL. To ascertain the impact of HLA-class I on EBV-latency antigen-specific immuno-dominance, we used a step-wise functional T-cell approach. In newly diagnosed EBV(+) cHL, the magnitude of ex vivo @entity25062 /2A-specific @entity405 (+) T-cell responses was elevated in @entity1529 *02(+) @entity1 . Furthermore, in a controlled in vitro assay, LMP2A-specific @entity405 (+) T-cells from healthy @entity1529 *02 heterozygotes expanded to a greater extent with @entity1529 *02-restricted compared to non- @entity1529 *02-restricted cell lines. In an extensive analysis of HLA-class I-restricted immunity, immuno-dominant EBNA3A/3B/3C-specific @entity405 (+) T-cell responses were stimulated by numerous HLA-class I molecules, whereas the sub-dominant @entity25062 /2A-specific responses were largely confined to @entity1529 *02. Our results demonstrate that @entity1529 *02 mediates a modest, but nonetheless stronger, EBV-specific @entity405 (+) T-cell response than non- @entity1529 *02 alleles, an effect confined to EBV-latency-II antigens. Thus, the protective effect of @entity1529 *02 against EBV(+) cHL is not a surrogate association, but reflects the impact of HLA-class I on EBV-latency-II antigen-specific @entity405 (+) T-cell hierarchies. This article is protected by copyright. All rights reserved.
