T CELL RECEPTOR-LIKE/T8/HLA INTERACTIONS IN RECOGNITION

这项提案的主要目的是研究分子 Ⅰ类重链与两细胞表面相互作用 可能参与MHCrestricted抗原的组分 T细胞识别：i）在Sezary上发现的38 kDa分子 白血病和同种异体活化T细胞;和ii）存在于 胸腺细胞和成熟T细胞的亚群。 我们的初步结果表明，β 2 M-免费的HLA重 链非共价结合的38 kDa分子上发现的 Sezary白血病和正常同种异体活化T细胞的表面。 该38-43 kDa异二聚体的38 kDa组分显示 与“经典”α-β链的β链结构同源 T细胞受体在相同的白血病细胞上表达。 就像阿尔法- β受体，38-43 kDa的异二聚体与T3相关 分子复合体 T细胞上表达的38 kDa分子 来自三种不同来源的白血病细胞在其 分子量和pI，从而表明38个克隆的性质， kDa分子。 因此，我们假设这个38 kDa的分子 可能参与T细胞识别抗原的过程。 同样，T8分子被认为参与了MHC-1的表达。 限制T细胞识别。 因此，我们的结果 表明在正常外周血T细胞表面， T8分子与无β 2 M的HLA非共价结合 重链 为了确定这些分子复合物 由HLA重链在T细胞表面形成的抗体具有功能性 结果，我们建议通过血清学， 遗传学和生物化学手段。 更具体地说，我们建议 以下课程的研究：1. 产生单克隆和 白血病细胞上表达的抗38 kDa分子的异源抗体 和正常的同种活化T细胞。 2.克隆编码 38 kDa分子。 3. 进一步说明关联 HLA和38 kDa分子之间的关系。 4.鉴定 细胞免疫功能特性之间的相关性 和38 kDa分子的表达。 5.生化 T8-HLA分子复合物的表征。 6. T8-HLA分子复合物存在的测定 T8阳性细胞的不同功能亚群。

The main objective of this proposal is to study molecular interactions between Class I heacy chain and two cell surface components possibly involved in MHCrestricted antigen recognition by T cells: i) a 38 kDa molecule found on Sezary leukemia and alloactivated T cells; and ii) T8 molecule present on a subpopulation of thymocytes and mature T cells. Our preliminary results suggest that beta 2M-free HLA heavy chain is noncovalently associated with a 38 kDa molecule found on the surface of Sezary leukemia and normal alloactivated T cells. The 38 kDa component of this 38-43 kDa heterodimer displays structural homology to the beta-chain of a "classical" alpha-beta T cell receptor expressed on the same leukemia cells. Like alpha- beta receptor, the 38-43 kDa heterodimer is associated with T3 molecular complex. The 38 kDa molecules expressed on T leukemia cells from three different sources vary in their molecular mass and pI thus suggesting a clonal nature of the 38 kDa molecule. We assume therefore that this 38kDa molecule may be involved in the process of antigen recognition by T cells. Likewise, the T8 molecule is thought to be involved in MHC- restricted T cell recognition. In accordance with this, our results indicate that on the surface of normal peripheral blood T cells the T8 molecule is noncovalently associated with beta 2M-free HLA heavy chain. To determine whether these molecular complexes formed on the T cell surface by HLA heavy chains have functional consequences, we propose to investigate them by serological, genetical and biochemical means. More specifically, we suggest the following course of studies: 1. Generation of monoclonal and heteroantibodies against 38 kDa molecule expressed on leukemia and normal alloactivated T cells. 2. Cloning the gene coding for the 38 kDa molecule. 3. Further elucidation of the association between HLA and 38 kDa molecules. 4. Identification of correlation between cellular immune functional characteristics and expression of 38 kDa molecule. 5. Biochemical characterization of the T8-HLA molecular complex. 6. Determination of the presence of T8-HLA molecular complexes in different functional subsets of T8-positive cells.