期刊
JOURNAL OF IMMUNOLOGY
卷 187, 期 2, 页码 684-691出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1100316
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资金
- Medical Research Council (U.K.)
- Li Ka Shing Foundation
- Royal Society (U.K.)
- Beijing Natural Science Foundation
- Beijing Talents Building Projects [PYZZ091016001765]
- Beijing Municipal Health Bureau [QN2009-29]
- Beijing Fengtai Health Bureau
- Beijing Municipal Science and Technology Commission [D09050703590904, D09050703560903, D09050703590901]
- China National Science and Technology Key Program [2008ZX10001-003, 2008ZX10001-006, 2008ZX10001-001]
- Drs. Richard Charles and Esther Yewpick Lee Charitable Foundation
- Grants-in-Aid for Scientific Research [10J56531] Funding Source: KAKEN
- Medical Research Council [G0801751, G1001046, MC_U137884177, G0600520, G1000800f, G1000800j] Funding Source: researchfish
- MRC [G1001046, G0600520, MC_U137884177, G0801751] Funding Source: UKRI
Polymorphism in the HLA region of a chromosome is the major source of host genetic variability in HIV-1 outcome, but there is limited understanding of the mechanisms underlying the beneficial effect of protective class I alleles such as HLA-B57, -B27, and -B51. Taking advantage of a unique cohort infected with clade B' HIV-1 through contaminated blood, in which many variables such as the length of infection, the infecting viral strain, and host genetic background are controlled, we performed a comprehensive study to understand HLA-B51-associated HIV-1 control. We focused on the T cell responses against three dominant HLA-B51-restricted epitopes: Gag327-345(NI9) NANPDCKTI, Pol743-751(LI9) LPPVVAKEI, and Pol283-289(TI8) TAFTIPSI. Mutations in all three dominant epitopes were significantly associated with HLA-B51 in the cohort. A clear hierarchy in selection of epitope mutations was observed through epitope sequencing. L743I in position 1 of epitope LI9 was seen in most B51(+) individuals, followed by V289X in position 8 of the TI8, and then, A328S, in position 2 of the NI9 epitope, was also seen in some B51(+) individuals. Good control of viral load and higher CD4(+) counts were significantly associated with at least one detectable T cell response to unmutated epitopes, whereas lower CD4(+) counts and higher viral loads were observed in patients who had developed escape mutations in all three epitopes or who lacked T cell responses specific to these epitope(s). We propose that patients with HLA-B51 benefit from having multiple layers of effective defense against the development of immune escape mutations. The Journal of Immunology, 2011, 187: 684-691.
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