Molecular and cellular analysis of human T lymphocytes expressing gamma delta T-cell receptor.
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)
Moretta
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Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Ciccone
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E
Ferrini
S
S
Pelicci
P G
PG
Mingari
M C
MC
Zeromski
J
J
Bottino
C
C
Grossi
C
C
Moretta
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003602:Cytotoxicity, Immunologic; D015329:Gene Rearrangement, T-Lymphocyte; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D005796:Genes; D006801:Humans; D008213:Lymphocyte Activation; D009928:Organ Specificity; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000648:ultrastructure
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta