Transplantation Antigens: Expression and Function

描述（由申请人提供）：先天性和适应性免疫应答之间的相互作用目前正在成为免疫学中的一个新课题，对医学科学具有潜在影响。在参与这些过程的许多不同分子中，有抗原呈递类IMHC家族，其协调NK细胞和T细胞应答并调节它们的相互作用。该建议的重点是非经典（Ib类）MHC，Qa-2，类似于Ia类和人类Ib类，HLA-G。具有潜在不同能力或调节免疫的多个基因和多个可变剪接转录物编码Qa-2。我们的实验室在定义肽结合特性、晶体结构和通过GPl连接的典型Qa-2在NK细胞抑制中的作用方面发挥了重要作用。我们现在计划利用我们过去的专业知识和试剂来（1）鉴定Qa-2的新亚型并确定其表达模式;（2）评估它们与先天免疫系统（NK细胞）组分的相互作用;（3）研究它们在肿瘤排斥反应期间诱导保护性适应性免疫应答的功能。要解决的具体假设包括肽负载的Qa-2参与NK和T细胞受体的概念，以及推测它们在消除应激/恶性转化细胞中发挥专门作用。

DESCRIPTION (provided by the applicant): Interplay between innate and adaptive immune response is currently emerging as a novel topic in immunology with a potential impact in medical sciences. Among many different molecules participating in these processes is the family of antigen-presenting class IMHC, which orchestrate NK cell and T cell responses and regulate their interactions. The focus of this proposal is the nonclassical (class Ib) MHC, Qa-2, similar to class la and to human class Ib, HLA-G. Multiple genes and multiple alternatively spliced transcripts with potentially different capabilities or regulating immunity encode Qa-2. Our laboratory played a major role in defining the peptide-binding properties, the crystal structure and the role in NK cell inhibition by GPl-linked, canonical Qa-2. We now plan to use our past expertise and reagents to (1) identify novel isoforms of Qa-2 and determine their expression patterns;(2) evaluate their interactions with components of the innate immune system (NK cells); and (3) study their function in inducing protective adaptive immune response during tumor rejection. The specific hypotheses to be addressed include the notion that peptide-loaded Qa-2 engage NK and T cell receptors and the speculation that they play a specialized role in elimination of stressed/malignantly-transformed cells.