scholarly journals Inhibition of MHC class II-restricted T cell response by Lyt-2 alloantigen.

1989 ◽  
Vol 170 (3) ◽  
pp. 901-912 ◽  
Author(s):  
O Kanagawa ◽  
R Maki
Keyword(s):  
T Cells ◽  
T Cell ◽  
Class Ii ◽  
Class I ◽  
Antigen Specificity ◽  
Class I Mhc ◽  
Cell Class ◽  
Class Ii Mhc ◽  
T Cell Clone ◽  
Antigen Interaction

T cell hybridomas were established by fusing a CD8+ V beta 8.1+ CTL clone and a CD4+ V beta 8.1+ helper T lymphocyte (HTL) clone to the thymoma cell line BW5147. In contrast to the HTL x BW hybridomas, which retain the same antigen specificity as the original T cell clone, the CTL x BW hybridomas lost the class I MHC-restricted antigen response but acquired a new specificity to Mlsa antigen. Mlsa reactivity of CTL x BW hybridomas was shown to be mediated by the CTL TCR as assayed by inhibition using an anticlonotypic antibody to the CTL clone. Since hybridomas established with BW5147 lose CD8 expression, we have introduced the CD8 molecule into CTL x BW5147 hybridomas by gene transfection. The CD8+ V beta 8.1+ hybridoma was no longer capable of reacting to Mlsa antigen but exhibited the same antigen specificity as the parental CTL clone. Furthermore, the presence of the transfected CD8 molecule in the HTL x BW hybridomas was found to be inhibitory to class II MHC-restricted antigen reactivity. These results demonstrate that, besides its role in increasing the overall avidity of T cell-class I MHC/antigen interaction, the CD8 molecule inhibits T cell-class II MHC gene product/antigen interaction. This negative effect of the CD8 molecule on a class II MHC-restricted response may account for the failure of CD8+ T cells using either V beta 8.1 or V beta 6, which impart reactivity to the Mlsa antigen on CD4+ T cells, to respond to the Mlsa antigen.

scholarly journals Characterization of two distinct primary T cell populations that secrete interleukin 2 upon recognition of class I or class II major histocompatibility antigens.

1986 ◽  
Vol 163 (3) ◽  
pp. 603-619 ◽  
Author(s):  
T Mizuochi ◽  
S Ono ◽  
T R Malek ◽  
A Singer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Functional Response ◽  
Cell Subset ◽  
Class Ii ◽  
Class I ◽  
Cell Populations ◽  
Class I Mhc ◽  
T Cell Subset ◽  
Class Ii Mhc

This study has characterized the primary T cell subpopulations that secrete IL-2 in response to recognition of either class I or class II MHC encoded determinants. The addition to culture of anti-IL-2-R mAb inhibited the consumption of IL-2 by activated lymphocytes during the response period, permitting a much more accurate assessment of the amount of IL-2 produced in the response cultures. Using this response system, we found that primary T cell populations contain two IL-2-secreting T cell subsets that express reciprocal phenotypes and different MHC recognition specificities: an L3T4+, Lyt-2- T cell subset responsive to both class I and class II MHC alloantigens, and an L3T4-Lyt-2+ T cell subset responsive only to class I MHC alloantigens. The L3T4+ T cell subset expressed a broad functional response repertoire in that L3T4+ T cells were triggered to secrete IL-2 upon recognition of unmodified self-Ia determinants, allogeneic Ia determinants, and class I alloantigens presented by self-Ia determinants. The activation of L3T4+ IL-2-secreting T cells, even those responsive to class I MHC alloantigens, could be blocked completely by anti-Ia mAbs, confirming that the L3T4+ T cell subset was in fact class II restricted. In contrast, the Lvt-2+ T cell subset expressed a narrow functional response repertoire in that they were triggered to secrete IL-2 only in response to allogeneic class I MHC determinants, and were not triggered to secrete IL-2 even in response to TNP-modified self-MHC determinants. The specificity of Lyt-2+ IL-2-secreting T cells for class I MHC allodeterminants was confirmed by the observations that: (a) their activation could be blocked completely by anti-class I mAbs, (b) they could be triggered by Ia- cell lines which expressed class I MHC alloantigens and possessed accessory function, and (c) they responded to class I MHC alloantigens but failed to respond to class II MHC alloantigens, even in the presence of exogenously added second signals that circumvented the requirement for alloantigen-bearing accessory cells. Finally, the frequency of primary Lyt-2+ T cells that secreted IL-2 in response to class I (Kbm1) MHC alloantigens was shown to be only minimally lower than that of L3T4+ T cells that secreted IL-2 in response to class II (I-Abm12) MHC alloantigens.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals T Cell Activity Correlates with Oligomeric Peptide-Major Histocompatibility Complex Binding on T Cell Surface

2001 ◽  
Vol 276 (50) ◽  
pp. 47320-47328 ◽  
Author(s):  
Jennifer Buslepp ◽  
Rui Zhao ◽  
Debora Donnini ◽  
Douglas Loftus ◽  
Mohamed Saad ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Cell Clone ◽  
Cell Activity ◽  
Class I ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
T Cell Clone

Recognition of virally infected cells by CD8+T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotransplant) or different species (xenotransplant). AHIII12.2 is a murine T cell clone that recognizes the xenogeneic (human) class I MHC HLA-A2.1 molecule (A2) and the syngeneic murine class I MHC H-2 Dbmolecule (Db). Recognition of both A2 and Dbare peptide-dependent, and the sequences of the peptides recognized have been determined. Alterations in the antigenic peptides bound to A2 cause large changes in AHIII12.2 T cell responsiveness. Crystal structures of three representative peptides (agonist, null, and antagonist) bound to A2 partially explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a strong correlation is seen between T cell activity and the affinity of pMHC complexes for the T cell receptor. However, contrary to previous studies, we see similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface.

scholarly journals A Class II-Restricted CD8γ13 T-Cell Clone Protects During Chlamydia muridarum Genital Tract Infection

2020 ◽  
Vol 221 (11) ◽  
pp. 1895-1906
Author(s):  
Raymond M Johnson ◽  
Norma Olivares-Strank ◽  
Gang Peng
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cd8 T Cells ◽  
Genital Tract ◽  
Cell Clone ◽  
Class Ii ◽  
Class I ◽  
T Cell Clone ◽  
Tract Infections

Abstract Background The T-cell response to chlamydia genital tract infections in humans and mice is unusual because the majority of antigen-specific CD8 T cells are not class I restricted (referred to here as “unrestricted” or “atypical”). We previously reported that a subset of unrestricted murine chlamydia-specific CD8 T cells had a cytokine polarization pattern that included interferon (IFN)-γ and interleukin (IL)-13. Methods In this study, we investigated the transcriptome of CD8γ13 T cells, comparing them to Tc1 clones using microarray analysis. That study revealed that CD8γ13 polarization included IL-5 in addition to IFN-γ and IL-13. Adoptive transfer studies were performed with Tc1 clones and a CD8γ13 T-cell clone to determine whether either influenced bacterial clearance or immunopathology during Chlamydia muridarum genital tract infections. Results To our surprise, an adoptively transferred CD8γ13 T-cell clone was remarkably proficient at preventing chlamydia immunopathology, whereas the multifunctional Tc1 clone did not enhance clearance or significantly alter immunopathology. Mapping studies with major histocompatibility complex (MHC) class I- and class II-deficient splenocytes showed our previously published chlamydia-specific CD8 T-cell clones are MHC class II restricted. Conclusions The MHC class II-restricted CD8 T cells may play an important role in protection from intracellular pathogens that limit class I antigen presentation or diminish CD4 T-cell numbers or impair their function.

scholarly journals Genetic Dissection of Primary and Secondary Responses to a Widespread Natural Pathogen of the Gut,Eimeria vermiformis

2000 ◽  
Vol 68 (11) ◽  
pp. 6273-6280 ◽  
Author(s):  
Adrian L. Smith ◽  
Adrian C. Hayday
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Primary Response ◽  
Class I ◽  
Class Ii Mhc ◽  
Ifn Γ ◽  
Αβ T Cells

ABSTRACT Because most pathogens initially challenge the body at epithelial surfaces, it is important to dissect the mechanisms that underlie T-cell responses to infected epithelial cells in vivo. The coccidian parasites of the genus Eimeria are protozoan gut pathogens that elicit a potent, protective immune response in a wide range of host species. CD4+ αβ T cells and gamma interferon (IFN-γ) are centrally implicated in the primary immunoprotective response. To define any additional requirements for the primary response and to develop a comparison between the primary and the secondary response, we have studied Eimeria infections of a broad range of genetically altered mice. We find that a full-strength primary response depends on β2-microglobulin (class I major histocompatibility complex [MHC] and class II MHC and on IFN-γ and interleukin-6 (IL-6) but not on TAP1, perforin, IL-4, Fas ligand, or inducible nitric oxide synthetase. Indeed, MHC class II-deficient and IFN-γ-deficient mice are as susceptible to primary infection as mice deficient in all αβ T cells. Strikingly, the requirements for a highly effective αβ-T-cell-driven memory response are less stringent, requiring neither IFN-γ nor IL-6 nor class I MHC. The class II MHC dependence was also reduced, with adoptively transferable immunity developing in MHC class II−/− mice. Besides the improved depiction of an immune response to a natural gut pathogen, the finding that effective memory can be elicited in the absence of primary effector responses appears to create latitude in the design of vaccine strategies.

scholarly journals Identical peptides recognized by MHC class I- and II-restricted T cells.

1989 ◽  
Vol 170 (1) ◽  
pp. 279-289 ◽  
Author(s):  
D L Perkins ◽  
M Z Lai ◽  
J A Smith ◽  
M L Gefter
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Class Ii ◽  
Antigen Recognition ◽  
Class I ◽  
Single Class ◽  
Mhc Molecules ◽  
Cell Responses ◽  
Class Ii Mhc

Previous data from many groups show that both class I and class II-restricted T cells recognize short synthetic peptides in the context of their respective MHC molecules (9-18), all of the peptides described to date are restricted to only a single class of MHC molecules; however, structural homology between the class I and II MHC molecules and the use of similar TCRs by class I and II-restricted T cells suggest that antigen recognition mechanisms are similar in both systems. To directly compare antigen recognition in the two systems, we analyzed peptides for the ability to function in both a class I and II-restricted system and found that seven of seven individual peptides tested stimulate both class I and II-restricted T cell responses. In addition, two of the peptides can function in different species stimulating both human class I and murine class II T cell responses. Thus, the process of T cell recognition of antigen in the context of MHC molecules was highly conserved in evolution not only between the class I and class II MHC systems, but also between the murine and human species.

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 Local microbleeding facilitates IL-6– and IL-17–dependent arthritis in the absence of tissue antigen recognition by activated T cells

2011 ◽  
Vol 208 (1) ◽  
pp. 103-114 ◽  
Author(s):  
Masaaki Murakami ◽  
Yuko Okuyama ◽  
Hideki Ogura ◽  
Shogo Asano ◽  
Yasunobu Arima ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Antigen Recognition ◽  
Type I ◽  
Antigen Specificity ◽  
Class Ii Mhc ◽  
Cognate Antigen

Cognate antigen recognition by CD4+ T cells is thought to contribute to the tissue specificity of various autoimmune diseases, particularly those associated with class II MHC alleles. However, we show that localized class II MHC–dependent arthritis in F759 mice depends on local events that result in the accumulation of activated CD4+ T cells in the absence of cognate antigen recognition. In this model, transfer of in vitro polarized Th17 cells combined with the induction of experimental microbleeding resulted in CCL20 production, the accumulation of T cells in the joints, and local production of IL-6. Disease induction required IL-17A production by transferred T cells, IL-6 and CCL20 expression, and STAT3 signaling in type I collagen–expressing cells. Our data suggest a model in which the development of autoimmune disease in F759 mice depends on four events: CD4+ T cell activation regardless of antigen specificity, local events that induce T cell accumulation, enhanced sensitivity to T cell–derived cytokines in the tissue, and activation of IL-6 signaling in the tissue. This model provides a possible explanation for why tissue-specific antigens recognized by activated CD4+ T cells have not been identified in many autoimmune diseases, especially those associated with class II MHC molecules.

HLAs, TCRs, and KIRs, a Triumvirate of Human Cell-Mediated Immunity

2020 ◽  
Vol 89 (1) ◽  
pp. 717-739 ◽  
Author(s):  
Zakia Djaoud ◽  
Peter Parham
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
T Cell Receptors ◽  
Hla Class I ◽  
Class Ii ◽  
Class I ◽  
Antigenic Specificity ◽  
Class I Mhc ◽  
Cell Receptors

In all human cells, human leukocyte antigen (HLA) class I glycoproteins assemble with a peptide and take it to the cell surface for surveillance by lymphocytes. These include natural killer (NK) cells and γδ T cells of innate immunity and αβ T cells of adaptive immunity. In healthy cells, the presented peptides derive from human proteins, to which lymphocytes are tolerant. In pathogen-infected cells, HLA class I expression is perturbed. Reduced HLA class I expression is detected by KIR and CD94:NKG2A receptors of NK cells. Almost any change in peptide presentation can be detected by αβ CD8+ T cells. In responding to extracellular pathogens, HLA class II glycoproteins, expressed by specialized antigen-presenting cells, present peptides to αβ CD4+ T cells. In comparison to the families of major histocompatibility complex (MHC) class I, MHC class II and αβ T cell receptors, the antigenic specificity of the γδ T cell receptors is incompletely understood.

scholarly journals Constitutive CD8 expression allows inefficient maturation of CD4+ helper T cells in class II major histocompatibility complex mutant mice.

1994 ◽  
Vol 179 (6) ◽  
pp. 1997-2004 ◽  
Author(s):  
E Robey ◽  
A Itano ◽  
W C Fanslow ◽  
B J Fowlkes
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Class I ◽  
Major Histocompatibility ◽  
Cd4 Cells ◽  
Class I Mhc ◽  
Histocompatibility Complex ◽  
Class Ii Mhc

Although mature CD4+ T cells bear T cell receptors (TCRs) that recognize class II major histocompatibility complex (MHC) and mature CD8+ T cells bear TCRs that recognize class I MHC, it is possible that the initial commitment of an immature thymocyte to a CD4 or CD8 lineage is made without regard to the specificity of the TCR. According to this model, CD4+ cells with class I TCR do not mature because the CD8 coreceptor is required for class I MHC recognition and positive selection. If this model is correct, constitutive expression of CD8 should allow CD4+ T cells with class I-specific TCRs to develop. In this report, we show that mature peripheral CD4+ cells are present in class II MHC-deficient mice that express a constitutive CD8.1 transgene. These cells share a number of properties with the major class II MHC-selected CD4 population, including the ability to express CD40 ligand upon activation. Although mature CD4 cells are also detectable in the thymus of class II MHC mutant/CD8.1 transgenic mice, they represent a small fraction of the mature CD4 cells found in mice that express class II MHC. These results indicate that some T cells choose the CD4 helper lineage independent of their antigen receptor specificity; however, the inefficiency of generating class I-specific CD4 cells leaves open the possibility that an instructive signal generated upon MHC recognition may bias lineage commitment.

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