Immunology Coday,voL 8, No. 3, 1987 ,~ii ~......
processing, but m,ay also result from an effect on the transport of class II glycoproteins.
A non-MHC restricted T-cell receptor Paradoxically, of the studies of the T-cell receptor reported at the meeting, those which provoked the most interest were of the newly-defined -y-chain receptor, which may not be MHC-restricted in its ability to bind antigen. By now, the basic two-chain Ig-like structure of the oL, 13 T-cell receptor, with the associated CD3 polypeptides, is quite familiar. Recently a subpopulation of human T cells bearing the CD3 antigen has been isolated which expresses a novel receptor containing a subunit encoded by the -y-chain gene, previously only defined at the nucleic acid level. M. Brenner (Harvard)described elegant experiments leading to the isolation of a CDh3 ÷, CD4, 8-, subpopulation of human peripheral T lymphocytes from immunodeficiency patients which failed to react with a monoclonal antibody recognizing framework determinants of the o~, 13 T-cell receptor. Clones of these cells expanded in interleukin-2 (IL-2) proved to express no mRNA encoding the ~ or 13 subunits but did express ~/-chain mRNA. Antibodies to synthetic peptides corresponding to the amino acid sequence of the -y-chain predicted from cDNA clones proved to react with these cells and could be used to precipitate a heterodimeric molecule from the cloned cell populations. One subunit (55kDa) reacted directly with the anti -y-chain antibodies, and the associated 40kDa protein is presumed to represent a second subunit, named, naturally enough, 8. J. Allison (Berkeley) reported similar results, with slightly different molecular weight estimates for the subunits, which also clearly demonstrated that the -y,8 receptor is associated with the CD3 complex, as is the case for the o~,13 receptor. Extension of the story into the murine system was reported by J. Coligan (Bethesda), who similarly used antibodies to synthetic peptides with sequences inferred from murine -y-chain cDNA clones. As in humans, these antibodies proved to react with a minor subpopulation of T cells. This population was negative for both the Lyt 2 and L3T4 T-cell markers, the murine homologues of CD8 and CD4. Immunoprecipitation from radiolabeled thymocytes showed (
Icl~q7 l l,,i,.p~,I P,lli',~,iI,(~I:~,, ,." Ir*r'llr dqt'
(]l{~7
that the murine -y-chain had a molecular weight of 35 000 and was disulfide-bonded to a second 45 000 dalton subunit. The precise function of this newlydefined population of T-cells was the subject of debate but remains unknown. Brenner presented data showing that anti-CD3 antibodies will induce an increase in intracellular free calcium in ~/-chain-positive T-cell clones, and will also s.timulate them to exhibit non-specific cytotoxicity against human cell lines. These cells therefore have cytotoxic potential, but their natural targets have yet to be uncovered. In the same final session of the meeting, where the above: story of the T-cell ~/,8 receptor was recounted, M. Owen (London) described the molecular cloning and sequencing of the CD3 subunit, unfortunately still named the -y-chain, which is phosphorylated upon T-cell activation indicating a role for the
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,
:~~: i~ ¸
CD3 complex in trans-membrane signalling. He also reported the sequence of the CD2 (T11 ) molecule, which proved to exhibit some sequence homology with the 'immunoglobulin superfamily' and which can provide an alternative pathway for T-cell activation. This final session clearly demonstrated the speed with which the molecular details of T-cell recognition mechanisms are being uncovered.
References 1 Chestnut, R.W., Colon, S.M. and Grey, H.M (1982)J. Immunol. 128, 1764 2 Unanue, E.R.(1984) Annu. Rev. ImrnunoL 2,395 3 Streicher, H.C., Berkower, I.J., Bush, M. et al. (1984) Proc. Natl Acad. Sci. USA 81,6831
PeterCresswellis at the Departmentof Microbiology and Immunology, Duke University Medical Center,Durham,NC27710, USA
Proposed classification of leukocyteassociated cytolytic molecules The continuous discovery of leukocyteassociated cytolytic factors and the lack of a nomenclature system to accommodate them prompted the nomenc/at'J ~. committee of the Reticuloendothelial Society (RES) to sponsor a recent dry workshop on the topic*, which was attended by about 100, mainly American, scientists. Various cell types of the immune system can produce one or more molecules which are cytolytic for tumor cells1: natural killer cytotoxic factor (NKCF), perforins, cytolysins, lymphotoxin (LT), and tumor necrosis factor (TNF). *Theworkshopwas held ,n Denver,CO, USA,28 Septeml3er1986 The part
processing, but m,ay also result from an effect on the transport of class II glycoproteins.
A non-MHC restricted T-cell receptor Paradoxically, of the studies of the T-cell receptor reported at the meeting, those which provoked the most interest were of the newly-defined -y-chain receptor, which may not be MHC-restricted in its ability to bind antigen. By now, the basic two-chain Ig-like structure of the oL, 13 T-cell receptor, with the associated CD3 polypeptides, is quite familiar. Recently a subpopulation of human T cells bearing the CD3 antigen has been isolated which expresses a novel receptor containing a subunit encoded by the -y-chain gene, previously only defined at the nucleic acid level. M. Brenner (Harvard)described elegant experiments leading to the isolation of a CDh3 ÷, CD4, 8-, subpopulation of human peripheral T lymphocytes from immunodeficiency patients which failed to react with a monoclonal antibody recognizing framework determinants of the o~, 13 T-cell receptor. Clones of these cells expanded in interleukin-2 (IL-2) proved to express no mRNA encoding the ~ or 13 subunits but did express ~/-chain mRNA. Antibodies to synthetic peptides corresponding to the amino acid sequence of the -y-chain predicted from cDNA clones proved to react with these cells and could be used to precipitate a heterodimeric molecule from the cloned cell populations. One subunit (55kDa) reacted directly with the anti -y-chain antibodies, and the associated 40kDa protein is presumed to represent a second subunit, named, naturally enough, 8. J. Allison (Berkeley) reported similar results, with slightly different molecular weight estimates for the subunits, which also clearly demonstrated that the -y,8 receptor is associated with the CD3 complex, as is the case for the o~,13 receptor. Extension of the story into the murine system was reported by J. Coligan (Bethesda), who similarly used antibodies to synthetic peptides with sequences inferred from murine -y-chain cDNA clones. As in humans, these antibodies proved to react with a minor subpopulation of T cells. This population was negative for both the Lyt 2 and L3T4 T-cell markers, the murine homologues of CD8 and CD4. Immunoprecipitation from radiolabeled thymocytes showed (
Icl~q7 l l,,i,.p~,I P,lli',~,iI,(~I:~,, ,." Ir*r'llr dqt'
(]l{~7
that the murine -y-chain had a molecular weight of 35 000 and was disulfide-bonded to a second 45 000 dalton subunit. The precise function of this newlydefined population of T-cells was the subject of debate but remains unknown. Brenner presented data showing that anti-CD3 antibodies will induce an increase in intracellular free calcium in ~/-chain-positive T-cell clones, and will also s.timulate them to exhibit non-specific cytotoxicity against human cell lines. These cells therefore have cytotoxic potential, but their natural targets have yet to be uncovered. In the same final session of the meeting, where the above: story of the T-cell ~/,8 receptor was recounted, M. Owen (London) described the molecular cloning and sequencing of the CD3 subunit, unfortunately still named the -y-chain, which is phosphorylated upon T-cell activation indicating a role for the
,Ic}}Q ~7 ~(}.~
~
,
:~~: i~ ¸
CD3 complex in trans-membrane signalling. He also reported the sequence of the CD2 (T11 ) molecule, which proved to exhibit some sequence homology with the 'immunoglobulin superfamily' and which can provide an alternative pathway for T-cell activation. This final session clearly demonstrated the speed with which the molecular details of T-cell recognition mechanisms are being uncovered.
References 1 Chestnut, R.W., Colon, S.M. and Grey, H.M (1982)J. Immunol. 128, 1764 2 Unanue, E.R.(1984) Annu. Rev. ImrnunoL 2,395 3 Streicher, H.C., Berkower, I.J., Bush, M. et al. (1984) Proc. Natl Acad. Sci. USA 81,6831
PeterCresswellis at the Departmentof Microbiology and Immunology, Duke University Medical Center,Durham,NC27710, USA
Proposed classification of leukocyteassociated cytolytic molecules The continuous discovery of leukocyteassociated cytolytic factors and the lack of a nomenclature system to accommodate them prompted the nomenc/at'J ~. committee of the Reticuloendothelial Society (RES) to sponsor a recent dry workshop on the topic*, which was attended by about 100, mainly American, scientists. Various cell types of the immune system can produce one or more molecules which are cytolytic for tumor cells1: natural killer cytotoxic factor (NKCF), perforins, cytolysins, lymphotoxin (LT), and tumor necrosis factor (TNF). *Theworkshopwas held ,n Denver,CO, USA,28 Septeml3er1986 The part
