Transplantation Antigens: Expression and Function

描述(由申请人提供)：先天性免疫反应和获得性免疫反应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的影响。在参与这些过程的许多不同分子中，有一类是抗原提呈类IMHC，它协调NK细胞和T细胞的反应并调节它们的相互作用。这一提议的重点是非经典(Ib类)MHC，Qa-2，类似于La类，以及类似于人类Ib类，人类白细胞抗原-G。多个基因和多个可能具有不同功能或调节免疫的选择性剪接转录本编码Qa-2。我们的实验室在确定GPL连接的、规范的Qa-2与多肽结合的性质、晶体结构以及在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)鉴定新的Qa-2亚型并确定它们的表达模式；(2)评估它们与天然免疫系统(NK细胞)组件的相互作用；以及(3)研究它们在诱导肿瘤排斥反应期间保护性适应性免疫反应中的功能。需要解决的具体假设包括，载肽Qa-2与NK和T细胞受体结合的概念，以及它们在消除应激/恶性转化细胞方面发挥特殊作用的推测。

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.