Molecular and Cellular Analysis of Human T Lymphocytes Expressing γδ T‐Cell Receptor
Molecular and Cellular Analysis of Human T Lymphocytes Expressing γδ T‐Cell Receptor
复制标题
表达γT细胞受体的人T淋巴细胞的分子和细胞分析
作者:
Lorenzo Morctta;E. Ciccone;S. Ferrini;P. Pelicci;M. Mingari;J. Żeromski;C. Bottino;C. Grossi;A. Moretta
A minor subset of T lymphocytes expresses a CD3-associated TCR composed of gamma and delta chains. The majority of TCR gamma/delta+ cells lack surface CD4 and CD8 antigen and do not react with WT31 mAb. These negative criteria were utilized in early studies to identify TCR gamma/delta+ cells. More recently, mAb to TCR gamma/delta, selected in different laboratories, have permitted the direct identification of TCR gamma/delta+ cells and their subsets. TCR gamma/delta molecules were found to be heterogeneous in size and charge mobility. Two major forms of TCR gamma/delta could be identified that are characterized by the presence or absence of an inter-chain disulphide bond. Biochemical analysis originally suggested that a precise correlation existed between reactivity with BB3 or delta TCS1/A13 mAb and expression of a disulphide (C gamma 1-encoded) or non-disulphide linked (C gamma 2-encoded) form of TCR gamma/delta. However, more recent studies have indicated that these mAb react with the molecular product of V delta 2 or V delta 1, respectively, mAb directed to one or another form of TCR gamma/delta activate the functional program of the cell, leading to intracellular Ca++ mobilization, lymphokine production and triggering of the lytic machinery. Analysis of the target molecules for TCR gamma/delta-mediated recognition revealed that at least some TCR gamma/delta+ cells are capable of specific responses to (allo)antigen and that polymorphic determinants of class I molecules can be recognized (as shown by the specific lysis of P815 cells transfected with HLA-24 allele). Unlike TCR alpha/beta+ cells, TCR gamma/delta+ cells are homogeneously composed of cytolytic precursors, as shown by the analysis of a large panel of clones in both lectin-dependent and redirected killing assays. In spite of their LGL morphology, freshly isolated TCR gamma/delta+ cells do not lyse NK-sensitive targets but do so after exposure to rIL-2. A modest cytolytic activity, however, could be induced also in fresh cells by anti-TCR/CD3 mAb in a redirected killing assay. Analysis of the distribution of the subsets expressing different TCR gamma/delta types showed that BB3+ cells are prevalent in the peripheral blood and virtually absent in the thymus; in contrast, A13+ (delta TCS1+) cells represent the majority of TCR gamma/delta+ thymocytes. Electron microscopic analysis of fresh TCR gamma/delta+ cells showed an extended cytoplasm containing numerous electron-dense granules identifiable as primary lysosomes. Upon stimulation with IL-2, TCR gamma/delta+ cells, similar to other LAK cells, display an increase in their cytoplasmic granules together with a redistribution of cytoskeletal structures.(ABSTRACT TRUNCATED AT 400 WORDS)
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DOI:
10.1073/pnas.84.8.2430
发表时间:
1987
影响因子:
11.1
作者:
Stingl,G;Gunter,KC;Tschachler,E;Yamada,H;Lechler,RI;Yokoyama,WM;Steiner,G;Germain,RN;Shevach,EM
通讯作者:
Shevach,EM
DOI:
--
发表时间:
1989
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
作者:
Bucy,RP;Chen,CL;Cooper,MD
通讯作者:
Cooper,MD
DOI:
10.1126/science.2955517
发表时间:
1987
期刊:
Science (New York, N.Y.)
影响因子:
--
作者:
Krangel,MS;Band,H;Hata,S;McLean,J;Brenner,MB
通讯作者:
Brenner,MB
影响因子:
4.4
作者:
R. P. Bucy;C.-L. H. Chen;J. Cihak;U. Lösch;M D Cooper
通讯作者:
R. P. Bucy;C.-L. H. Chen;J. Cihak;U. Lösch;M D Cooper
影响因子:
64.8
作者:
Quertermous,T;Strauss,W;Murre,C;Dialynas,DP;Strominger,JL;Seidman,JG
通讯作者:
Seidman,JG