揭开人体抵抗艾滋病病毒之谜

一项最新研究发现，那些可以抵抗艾滋病毒的人，体内所含的一种基因令他们拥有一个更加强大的免疫系统。

研究发现，有一小部分人(大约每200名感染者中就有这样一个人)接触艾滋病毒后，发展成艾滋病的速度很慢，甚至不会患上这种致命疾病。以前的研究发现，很多天生具有艾滋病毒免疫能力的人，体内含有一种被称作HLA B57的基因。

在这项最新研究中美国研究人员发现，HLA B57促使身体产生更多强大的杀伤T细胞。杀伤T细胞是会对具有感染性的入侵者发起攻击的白细胞。与没有这种基因的人相比，那些拥有HLA B57的人体内含有大量可以束缚住艾滋病毒蛋白的T细胞。拥有HLA B57的人，体内的T细胞更有可能识别出代表艾滋病毒蛋白的细胞，其中包括在感染过程中产生的变异蛋白。

据马萨诸塞州总医院拉贡研究所、麻省理工学院和哈佛大学的研究人员说，这些发现或许有助于科学家研发出艾滋病疫苗，它引起的免疫响应，与具有HLA B57基因的人对艾滋病毒做出的免疫响应一样。

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Effects of thymic selection of the T-cell repertoire on HLA classI-associated
 control of HIV infection
Andrej Kosmrlj ^1,2,9, Elizabeth L. Read ^1,3,4,9, Ying Qi5, Todd M. Allen ¹, Marcus Altfeld ^1,
Steven G. Deeks ⁶, Florencia Pereyra ^1, Mary Carrington ^1,5,
Bruce D. Walker ^1,7 & Arup K. Chakraborty ^1,3,4,8

1.Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts 02114, USA
2.Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
3.Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
4.Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
5.Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA
6.University of California, San Francisco, California 94110, USA
7.Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA
8.Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
9.These authors contributed equally to this work.

【Abstract】Without therapy, most people infected with human immunodeficiency virus (HIV) ultimately progress to AIDS. Rare individuals (‘elite controllers’) maintain very low levels of HIV RNA without therapy, thereby making disease progression and transmission unlikely. Certain HLA class I alleles are markedly enriched in elite controllers, with the highest association observed for HLA-B57 (ref. 1). Because HLA molecules present viral peptides that activate CD8+ T cells, an immune-mediated mechanism is probably responsible for superior control of HIV. Here we describe how the peptide-binding characteristics of HLA-B57 molecules affect thymic development such that, compared to other HLA-restricted T cells, a larger fraction of the naive repertoire of B57-restricted clones recognizes a viral epitope, and these T cells are more cross-reactive to mutants of targeted epitopes. Our calculations predict that such a T-cell repertoire imposes strong immune pressure on immunodominant HIV epitopes and emergent mutants, thereby promoting efficient control of the virus. Supporting these predictions, in a large cohort of HLA-typed individuals, our experiments show that the relative ability of HLA-B alleles to control HIV correlates with their peptide-binding characteristics that affect thymic development. Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies.