Structural in variance of T4 molecules from T cell clone Of different antigen and major histocompatibility complex specificities

1985 ◽  
Vol 15 (3) ◽  
pp. 291-295 ◽  
Author(s):  
Peter H. Sayre ◽  
Ellis L. Reinherz
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Clone ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
T Cell Clone

scholarly journals Antigen recognition by a T cell clone outside the context of the major histocompatibility complex. A role for Mls in antigen presentation.

1984 ◽  
Vol 159 (1) ◽  
pp. 305-312 ◽  
Author(s):  
S J Waters ◽  
S D Waksal ◽  
G P Norton ◽  
C A Bona
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Clone ◽  
Antigen Recognition ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Differentiation Markers ◽  
Histocompatibility Complex ◽  
T Cell Clone

A T cell clone isolated from antigen-primed CB6/F1 mice was shown to proliferate to keyhole limpet hemocyanin (KLH) in the presence of irradiated syngeneic F1 spleen cells, as well as spleen cells from either parental strain (BALB/c and C57BL/6). The genetic restriction involved in this antigen-specific proliferation was mapped using BXD (C57BL/6 X DBA/2) recombinant inbred strains of mice to the Mls gene on chromosome one. To exclude the role of Ia antigens as the restricting determinants, monoclonal anti-Ia antibodies were used to block the in vitro proliferative response of this clone. Although anti-Iab and anti-Iad blocked the proliferation of this clone to KLH in the presence of irradiated spleen cells from either parent, this effect was shown to be dependent on Ia molecules passively absorbed by the T cell clone from the irradiated filler cells. Since the T clone expressed Thy-1.2 and Lyt-1+ differentiation markers, its helper activity was compared with other KLH carrier-specific clones in an in vitro antibody synthesis assay. The Mls-KLH-restricted T cell clone, in contrast to other carrier-specific, major histocompatibility complex (MHC)-restricted T cell clones, was unable to cooperate with trinitrophenyl (TNP)-primed B cells in the presence of TNP-KLH to generate an anti-TNP response. These experiments suggest that non-MHC determinants, such as autologous Mls gene products, may play a role in genetically restricted antigen recognition by T lymphocytes.

scholarly journals A rare cryptic translation product is presented by Kb major histocompatibility complex class I molecule to alloreactive T cells.

1995 ◽  
Vol 182 (6) ◽  
pp. 1739-1750 ◽  
Author(s):  
S Malarkannan ◽  
M Afkarian ◽  
N Shastri
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Clone ◽  
Receptor Occupancy ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Alloreactive T Cells ◽  
T Cell Clone

The identity of allogeneic peptide/major histocompatibility complex (MHC) complexes that elicit vigorous T cell responses has remained an interesting problem for both practical and theoretical reasons. Although a few abundant MHC class I-bound peptides have been purified and sequenced, identifying the unique T cell-stimulating peptides from among the thousands of existing peptides is still a very difficult undertaking. In this report, we identified the antigenic peptide that is recognized by an alloreactive bm1 anti-B6 T cell clone using a novel genetic strategy that is based upon measurement of T cell receptor occupancy in single T cells. Using lacZ-inducible T cells as a probe, we screened a splenic cDNA library in transiently transfected antigen-presenting cells (APCs) and isolated a cDNA clone that allowed expression of the appropriate peptide/Kb MHC complex in APC. The antigenic octapeptide (SVVEFSSL) exactly matched the consensus Kb MHC motif, but was surprisingly encoded by a non-ATG defined translation reading frame. Furthermore, the abundance of the naturally processed analog in untransfected cells was estimated to be <10 copies per cell. These results illustrate a novel strategy for identifying T cell-stimulating antigens in general and directly show that alloreactive T cells can respond to rather rare peptide/MHC complexes. These results also suggest that the total pool of processed peptides expressed on the APC surface may include those generated by cryptic translation of normally expressed transcripts.

Recognition of the HLA class II-peptide complex by T-cell receptor: reversal of major histocompatibility complex restriction of a T-cell clone by a point mutation in the peptide determinant

1989 ◽  
Vol 323 (1217) ◽  
pp. 553-564 ◽  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Clone ◽  
Class Ii ◽  
Hla Class Ii ◽  
Helical Conformation ◽  
Major Histocompatibility ◽  
Peptide Complex ◽  
Histocompatibility Complex ◽  
T Cell Clone

Recognition of the HLA DR-peptide complex by an influenza haemagglutinin-specific T-cell clone was examined by assaying a variety of peptide analogues for their ability to be recognized. Consistent with earlier experiments arguing that the peptide blinds the restriction element in a helical conformation, acetylation of the amino terminus and amidation of the carboxy terminus of the natural determinant (residues 307-319) resulted in a peptide that exhibited both greater propensity to form a helix, as judged by circular dichroism, and the ability to stimulate the clone at concentrations approximately two orders of magnitude lower than the native sequence. The peptide was modelled into the potential antigen-combining site of HLA class II based on the ability of analogues containing point mutations to stimulate the T-cell clone. The working model was initially tested by examining the ability of Epstein-Barr-transformed B-cell lines expressing in different DR4 subtypes to present the native haemagglutinin sequence and analogues to the clone. The different alleles could be categorized as high, intermediate, or low responders based on the resulting proliferation. DR4 dw 15 was a high-responding allele, dw 4, 13, and 14 were intermediate-responding alleles, whereas dw 10 was a low responder. Mutation of Gin to Arg at 312 in the haemagglutim n sequence converted the high and intermediate responders to non-responders, while turning the low-responding allele into an intermediate responder. Potential explanations for these effects are discussed in the context of the model of the complex between peptide and the major histocompatibility complex.

scholarly journals Clone-specific T cell receptor antagonists of major histocompatibility complex class I-restricted cytotoxic T cells.

1993 ◽  
Vol 177 (6) ◽  
pp. 1541-1550 ◽  
Author(s):  
S C Jameson ◽  
F R Carbone ◽  
M J Bevan
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
T Cell Clone

A previous report showed that the proliferative response of helper T cells to class II major histocompatibility complex (MHC)-restricted antigens can be inhibited by analogues of the antigen, which act as T cell receptor (TCR) antagonists. Here we define and analyze peptide variants that antagonize various functions of class I MHC-restricted cytotoxic T lymphocyte (CTL) clones. Of 64 variants at individual TCR contact sites of the Kb-restricted octamer peptide ovalbumin257-264 (OVAp), a very high proportion (40%) antagonized lysis by three OVAp-specific CTL clones. This effect was highly clone specific, since many antagonists for one T cell clone have differential effects on another. We show that this inhibition of CTL function is not a result of T cell-T cell interaction, precluding veto-like phenomena as a mechanism for antagonism. Moreover, we present evidence for direct interaction between the TCR and antagonist-MHC complexes. In further analysis of the T cell response, we found that serine esterase release and cytokine production are susceptible to TCR antagonism similarly to lysis. Ca2+ flux, an early event in signaling, is also inhibited by antagonists but may be more resistant to the antagonist effect than downstream responses.

scholarly journals The Recognition of the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule, T10, by the γδ T Cell, G8

1997 ◽  
Vol 185 (7) ◽  
pp. 1223-1230 ◽  
Author(s):  
Michael P. Crowley ◽  
Ziv Reich ◽  
Nasim Mavaddat ◽  
John D. Altman ◽  
Yueh-hsiu Chien
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Class I ◽  
Γδ T Cell ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
T Cell Clone

Recent studies have shown that many nonclassical major histocompatibility complex (MHC) (class Ib) molecules have distinct antigen-binding capabilities, including the binding of nonpeptide moieties and the binding of peptides that are different from those bound to classical MHC molecules. Here, we show that one of the H-2T region–encoded molecules, T10, when produced in Escherichia coli, can be folded in vitro with β2-microglobulin (β2m) to form a stable heterodimer in the absence of peptide or nonpeptide moieties. This heterodimer can be recognized by specific antibodies and is stimulatory to the γδ T cell clone, G8. Circular dichroism analysis indicates that T10/β2m has structural features distinct from those of classical MHC class I molecules. These results suggest a new way for MHC-like molecules to adopt a peptide-free structure and to function in the immune system.

scholarly journals Major Histocompatibility Complex Class II Molecules Can Protect from Diabetes by Positively Selecting T Cells with Additional Specificities

1998 ◽  
Vol 187 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Fred Lühder ◽  
Jonathan Katz ◽  
Christophe Benoist ◽  
Diane Mathis
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Clonal Deletion ◽  
Histocompatibility Complex ◽  
T Cell Clone ◽  
B Mice

Insulin-dependent diabetes is heavily influenced by genes encoded within the major histocompatibility complex (MHC), positively by some class II alleles and negatively by others. We have explored the mechanism of MHC class II–mediated protection from diabetes using a mouse model carrying the rearranged T cell receptor (TCR) transgenes from a diabetogenic T cell clone derived from a nonobese diabetic mouse. BDC2.5 TCR transgenics with C57Bl/6 background genes and two doses of the H-2g7 allele exhibited strong insulitis at ∼3 wk of age and most developed diabetes a few weeks later. When one of the H-2g7 alleles was replaced by H-2b, insulitis was still severe and only slightly delayed, but diabetes was markedly inhibited in both its penetrance and time of onset. The protective effect was mediated by the Aβb gene, and did not merely reflect haplozygosity of the Aβg7 gene. The only differences we observed in the T cell compartments of g7/g7 and g7/b mice were a decrease in CD4+ cells displaying the transgene-encoded TCR and an increase in cells expressing endogenously encoded TCR α-chains. When the synthesis of endogenously encoded α-chains was prevented, the g7/b animals were no longer protected from diabetes. g7/b mice did not have a general defect in the production of Ag7-restricted T cells, and antigen-presenting cells from g7/b animals were as effective as those from g7/g7 mice in stimulating Ag7-restricted T cell hybridomas. These results argue against mechanisms of protection involving clonal deletion or anergization of diabetogenic T cells, or one depending on capture of potentially pathogenic Ag7-restricted epitopes by Ab molecules. Rather, they support a mechanism based on MHC class II–mediated positive selection of T cells expressing additional specificities.

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