Human T lymphocytes expressing gamma/delta T cell antigen receptor.
The majority of mature T lymphocytes express CD3-associated antigen receptor molecules (TCR) formed by alpha and beta chains. Recently, a minor subset has been identified that expresses a different CD3-associated heterodimer composed of gamma and delta chains. The TCR gamma/delta+ cell subset differs from conventional T cells for a number of phenotypic and functional characteristics. The simultaneous lack of both CD4 and CD8 antigens allows to greatly enrich TCR gamma/delta+ cells (by monoclonal antibodies and complement). Cloning of CD4-8- peripheral blood lymphocytes, under limiting dilution conditions, revealed that they are homogeneously composed of cytolytic cells which, in most instances, lyse tumor target cells. The formal proof has been provided that TCR gamma/delta+ cells are able to recognize antigens. Indeed they proliferated in response to allogeneic cells in mixed lymphocyte culture (MLC) and MLC-derived TCR gamma/delta+ cells specifically lysed PHA-induced blast cells bearing the stimulating alloantigens. The use of different monoclonal antibodies specific for TCR gamma/delta molecules allowed to identify two distinct subsets which bound BB3 and delta-TCS-1 mAbs, respectively. The BB3-reactive TCR molecules were represented by C gamma 1-encoded disulfide-linked heterodimers, whereas delta-TCS-1 reacted with C gamma 2-encoded nondisulfide-linked molecules. Both BB3 and delta-TCS-1 mAb induced activation of cloned cells expressing the corresponding antigenic determinants (as assessed by measurements of intracellular Ca2+ and lymphokine production or cytolytic activity). Analysis of the unfrequent delta-TCS-1+ clones which express surface CD8 molecules revealed that the "heavy" 55 kDa form of (C gamma 2-encoded) gamma chain is selectively expressed by this cell type. Analysis of the distribution of subsets expressing different TCR gamma/delta isotypes showed that the C gamma 1-encoded, BB3-reactive form is prevalent in the peripheral blood, but virtually absent in the thymus. In contrast, cells expressing the C gamma 2-encoded, delta-TCS-1 reactive form are relatively unfrequent in peripheral blood, but represent the majority of TCR gamma/delta+ thymocytes. In addition, upon culture in rIL-2, approximately half of the delta-TCS-1+ thymocytes expressed CD8 antigen, thus providing further evidence that major differences exist in the distribution of TCR gamma/delta+ subsets in thymus and in peripheral blood.
Moretta
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L
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Ciccone
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E
Mingari
M C
MC
Bottino
C
C
Ferrini
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S
Tambussi
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G
Melioli
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G
Grossi
C E
CE
Moretta
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D000911:Antibodies, Monoclonal / Q000276:immunology; D006801:Humans; D010641:Phenotype; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta