GENETICS OF T-LYMPHOCYTE ANTIGEN RECEPTORS

这项拨款申请描述了旨在 实现对1)T细胞识别的详细了解 抗原和2)发生在胸腺中的发育事件 在T细胞个体发育过程中。考虑到这些目标，我们正在研究 T细胞受体(TCR)谱系的差异 在MHC不同品系的小鼠之间。我们也是 第二类T细胞受体(TCR)谱系的特征 同种异体抗原I-Abm12和1类同种异体抗原Db。这个 这项赠款申请的具体目标如下。 具体目标1：了解Vβ5的数量是如何- 在B10(H-2b)和B10(H-2k)中确定了T细胞的表达 老鼠。 具体目标2：继续我们对T细胞受体的研究 2类同种异体抗原I-Abm12的谱系。 具体目标3：确定对人体健康至关重要的氨基酸残基 利用定点定位技术研究同种异体反应性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 根据其对抗原的亲和力进行选择(即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?)