GENETICS OF T-LYMPHOCYTE ANTIGEN RECEPTORS

这份拨款申请描述了旨在 1）T细胞识别， 抗原和2）胸腺中发生的发育事件 在T细胞个体发育过程中。 带着这些目标，我们正在研究 T细胞受体（TCR）库的差异， 不同品系的小鼠之间的差异 我们也 将T细胞受体（TCR）库表征为2类 同种异体抗原I-Abm 12和1类同种异体抗原Db。 的 申请拨款的具体目的如下。 具体目标1：了解V β 5- 在B10（H-2b）和B10.BR（H-2k）中测定表达T细胞的 小鼠 具体目标2：继续研究T细胞受体 2类同种异体抗原I-Abm 12的所有组成部分。 具体目标3：确定对蛋白质的合成至关重要的氨基酸残基。 同种异体反应性T细胞受体的特异性 诱变 具体目标4：确定同种异体反应性T细胞是否可以 基于它们对抗原的亲和力进行选择（即可以T- 细胞经历亲和力成熟？）

This grant application describes experiments that are aimed at achieving a detailed understanding of 1) T-cell recognition of antigens and 2) the developmental events that occur in the thymus during T-cell ontogeny. With these goals in mind, we are studying differences in the T-cell receptor (TCR) repertoire that occur between MHC-disparate strains of mice. We are also characterizing the T-cell receptor (TCR) repertoire to a class 2 alloantigen, I-Abm12, and to a class 1 alloantigen, Db. The specific aims of this grant application are stated below. Specific Aim 1: To understand how the number of V beta 5- expressing T-cells is determined in B10 (H-2b) and B10.BR (H-2k) mice. Specific Aim 2: To continue our studies of the T-cell receptor repertoire to the class 2 alloantigen, I-Abm12. Specific Aim 3: To define the amino acid residues critical to the specificity of an alloreactive T-cell receptor using site directed mutagenesis. Specific Aim 4: To determine whether alloreactive T-cells can undergo selection based on their affinity for antigen (i.e. can T- cells undergo affinity maturation?)