Variation in the risk and severity of many autoimmune diseases, malignancies and infections is strongly associated with polymorphisms in the HLA class I loci. These genetic associations provide a powerful opportunity for understanding the etiology of human disease. HLA class I associations are often interpreted in the light of 'protective' or 'detrimental' CD8⁺ T cell responses which are restricted by the host HLA class I allotype. However, given the diverse receptors which are bound by HLA class I molecules, alternative interpretations are possible. As well as binding T cell receptors on CD8⁺ T cells, HLA class I molecules are important ligands for inhibitory and activating killer immunoglobulin-like receptors (KIRs) which are found on natural killer cells and some T cells; for the CD94:NKG2 family of receptors also expressed mainly by NK cells and for leukocyte immunoglobulin-like receptors (LILRs) on myeloid cells. The aim of this study is to develop an immunogenetic approach for identifying and quantifying the relative contribution of different receptor-ligand interactions to a given HLA class I disease association and then to use this approach to investigate the immune interactions underlying HLA class I disease associations in three viral infections: Human T cell Leukemia Virus type 1, Human Immunodeficiency Virus type 1 and Hepatitis C Virus as well as in the inflammatory condition Crohn's disease.

中文翻译：

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识别HLA I类疾病关联的免疫相互作用

许多自身免疫性疾病，恶性肿瘤和感染的风险和严重性差异与HLA I类位点的多态性密切相关。这些遗传关联为了解人类疾病的病因提供了强大的机会。HLA I类关联通常是根据受宿主HLA I类同种异型限制的“保护性”或“有害” CD8 ⁺ T细胞反应来解释的。但是，考虑到受HLA I类分子结合的各种受体，可能会有其他解释。以及结合CD8 ⁺上的T细胞受体HLA I类分子T细胞是抑制和激活自然杀伤细胞和某些T细胞上发现的杀伤性免疫球蛋白样受体（KIR）的重要配体；CD94：NKG2受体家族也主要由NK细胞表达，髓样细胞上的白细胞免疫球蛋白样受体（LILR）也表达。这项研究的目的是开发一种免疫遗传学方法，以鉴定和量化不同受体-配体相互作用对给定的HLA I类疾病协会的相对贡献，然后使用这种方法研究HLA I类疾病协会中潜在的免疫相互作用。三种病毒感染：1型人T细胞白血病病毒，1型人免疫缺陷病毒和丙型肝炎病毒以及处于炎症状态的克罗恩病。