scholarly journals Novel Role of CD8+ T Cells and Major Histocompatibility Complex Class I Genes in the Generation of Protective CD4+ Th1 Responses during Retrovirus Infection in Mice

2002 ◽  
Vol 76 (16) ◽  
pp. 7942-7948 ◽  
Author(s):  
Karin E. Peterson ◽  
Ingunn Stromnes ◽  
Ron Messer ◽  
Kim Hasenkrug ◽  
Bruce Chesebro
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
T Cell Responses ◽  
Class I ◽  
Major Histocompatibility ◽  
Cell Responses ◽  
Histocompatibility Complex

ABSTRACT CD4+ Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8+ T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responder H-2b allele at major histocompatibility complex (MHC) class II loci, a single H-2Db MHC class I allele was sufficient for the development of a CD4+ Th1 response to FV. This effect of H-2Db on CD4+ T-cell responses was dependent on CD8+ T cells, as demonstrated by depletion studies. A direct effect of CD8+ T-cell help in the development of CD4+ Th1 responses to FV was also shown in vaccine studies. Vaccination of nonresponder H-2a/a mice induced FV-specific responses of H-2Dd -restricted CD8+ cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8+ T cells to naive H-2a/a mice prior to infection resulted in the generation of FV-specific CD4+ Th1 responses. This novel helper effect of CD8+ T cells could be an important mechanism in the development of CD4+ Th1 responses following vaccinations that induce CD8+ CTL responses. The ability of MHC class I genes to facilitate CD4+ Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.

Myofiber Expression of Class I Major Histocompatibility Complex Accompanied by CD8+ T-cell-associated Myofiber Injury in a Case of Canine Polymyositis

2002 ◽  
Vol 39 (4) ◽  
pp. 512-515 ◽  
Author(s):  
T. Morita ◽  
A. Shimada ◽  
S. Yashiro ◽  
T. Takeuchi ◽  
Y. Hikasa ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Plasma Cells ◽  
Early Stage ◽  
Cd8 T Cell ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

A 7-year-old female Labrador Retriever dog showed extreme muscular weakness, muscle wasting, dysbasia, and mild dysphagia. An elevated value of creatine kinase (335 IU/liter) in the serum was detected. Electromyographic findings included increased insertional activity, fibrillation potentials, and bizarre high-frequency repetitive potentials. Histopathologic examination of skeletal muscles revealed myofiber necrosis and phagocytosis, regeneration of myofibers, and perivascular, perimysial, and endomysial infiltrations of lymphocytes, macrophages and plasma cells. Immunohistochemical evaluation demonstrated that infiltrative cells in the early stage of myositis were CD8+ T-cells and that an increased expression of major histocompatibility complex (MHC) class I was apparent on the surface of nonnecrotic muscle fibers. In contrast, many CD3+ cells (T cells) and HLA-DR-positive macrophages and B lymphocytes were found in the severely affected areas. These results suggest that both expression of MHC class I and CD8+ T-cell infiltration may play an important role in initiation of myositis. These histopathologic findings resemble those reported in naturally occurring polymyositis in humans.

scholarly journals Analysis of Pigtail Macaque Major Histocompatibility Complex Class I Molecules Presenting Immunodominant Simian Immunodeficiency Virus Epitopes

2005 ◽  
Vol 79 (2) ◽  
pp. 684-695 ◽  
Author(s):  
Miranda Z. Smith ◽  
C. Jane Dale ◽  
Robert De Rose ◽  
Ivan Stratov ◽  
Caroline S. Fernandez ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
T Cell Responses ◽  
Class I ◽  
Pigtail Macaque ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Pigtail Macaques

ABSTRACT Successful human immunodeficiency virus (HIV) vaccines will need to induce effective T-cell immunity. We studied immunodominant simian immunodeficiency virus (SIV) Gag-specific T-cell responses and their restricting major histocompatibility complex (MHC) class I alleles in pigtail macaques (Macaca nemestrina), an increasingly common primate model for the study of HIV infection of humans. CD8+ T-cell responses to an SIV epitope, Gag164 - 172KP9, were present in at least 15 of 36 outbred pigtail macaques. The immunodominant KP9-specific response accounted for the majority (mean, 63%) of the SIV Gag response. Sequencing from six macaques identified 7 new Mane-A and 13 new Mane-B MHC class I alleles. One new allele, Mane-A*10, was common to four macaques that responded to the KP9 epitope. We adapted reference strand-mediated conformational analysis (RSCA) to MHC class I genotype M. nemestrina. Mane-A*10 was detected in macaques presenting KP9 studied by RSCA but was absent from non-KP9-presenting macaques. Expressed on class I-deficient cells, Mane-A*10, but not other pigtail macaque MHC class I molecules, efficiently presented KP9 to responder T cells, confirming that Mane-A*10 restricts the KP9 epitope. Importantly, naïve pigtail macaques infected with SIVmac251 that respond to KP9 had significantly reduced plasma SIV viral levels (log10 0.87 copies/ml; P = 0.025) compared to those of macaques not responding to KP9. The identification of this common M. nemestrina MHC class I allele restricting a functionally important immunodominant SIV Gag epitope establishes a basis for studying CD8+ T-cell responses against AIDS in an important, widely available nonhuman primate species.

scholarly journals Major Histocompatibility Complex Class I Gene Controls the Generation of Gamma Interferon-Producing CD4+and CD8+ T Cells Important for Recovery from Friend Retrovirus-Induced Leukemia

2000 ◽  
Vol 74 (11) ◽  
pp. 5363-5367 ◽  
Author(s):  
Karin E. Peterson ◽  
Michihiro Iwashiro ◽  
Kim J. Hasenkrug ◽  
Bruce Chesebro
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Gamma Interferon ◽  
Class I ◽  
Major Histocompatibility ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Ifn Γ

ABSTRACT Recovery from leukemia induced by Friend virus complex (FV) requires strong CD4+ helper, CD8+ cytotoxic T-lymphocyte, and B-cell responses. The development of these immune responses is dependent on the major histocompatibility complex (MHC) (H-2) genotype of the mouse. InH-2b/b mice, which spontaneously recover from FV-induced erythroleukemia, neutralization of gamma interferon (IFN-γ) in vivo inhibited recovery, which indicated that IFN-γ was a necessary component of the immune response to FV. Furthermore, inH-2b/b mice, high numbers of IFN-γ-producing cells were detected after FV infection, whereas inH-2a/b mice, which have a low-recovery phenotype, only low numbers of IFN-γ-producing cells were detected. Similarly, H-2bm14/b mice, which cannot recover from FV infection due to a point mutation in one allele of theH-2Db gene, also had low numbers of IFN-γ-producing T cells. Surprisingly, this effect was observed for both CD8+ and CD4+ T cells. These findings reveal a novel influence of MHC class I genes on CD4+T-cell responses to viral infection. Furthermore, the influence of MHC class I genotype on the generation of both IFN-γ-producing CD4+ and CD8+ T cells helps explain the major impact of the H-2D gene on recovery from FV disease.

scholarly journals CD8+ T cell response to Mls-1a determinants involves major histocompatibility complex class II molecules.

1991 ◽  
Vol 173 (3) ◽  
pp. 779-782 ◽  
Author(s):  
Y Chvatchko ◽  
H R MacDonald
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Class Ii ◽  
T Cell Response ◽  
Major Histocompatibility ◽  
Cell Responses ◽  
Histocompatibility Complex

Recent studies indicate that both CD4+ and CD8+ T lymphocytes proliferate in vitro in response to Mls-1a-encoded determinants. Using both immunogenetic and antibody blocking approaches we show here that Mls-1a responses of both subsets require expression of major histocompatibility complex (MHC) class II molecules (I-A and/or I-E) by the stimulator cells. Furthermore, CD8+ T cell responses to Mls-1a/class II MHC do not require (and are in fact inhibited by) the presence of functional CD8 molecules. Taken together, our data underscore the dramatic differences between CD8+ T cell responses to conventional peptide antigens as opposed to "superantigens" such as Mls-1a.

scholarly journals Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells.

1992 ◽  
Vol 176 (1) ◽  
pp. 89-97 ◽  
Author(s):  
N Killeen ◽  
A Moriarty ◽  
H S Teh ◽  
D R Littman
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Negative Selection ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules ◽  
Selection Of

The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes.

Mouse Schwann cells activate MHC class I and II restricted T-cell responses, but require external peptide processing for MHC class II presentation

2010 ◽  
Vol 37 (2) ◽  
pp. 483-490 ◽  
Author(s):  
Gerd Meyer zu Hörste ◽  
Holger Heidenreich ◽  
Anne K. Mausberg ◽  
Helmar C. Lehmann ◽  
Anneloor L.M.A. ten Asbroek ◽  
...  
Keyword(s):  
T Cell ◽  
Schwann Cells ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
T Cell Responses ◽  
Class Ii ◽  
Class I ◽  
Peptide Processing ◽  
Cell Responses

scholarly journals Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance

2002 ◽  
Vol 196 (12) ◽  
pp. 1627-1638 ◽  
Author(s):  
Laura Bonifaz ◽  
David Bonnyay ◽  
Karsten Mahnke ◽  
Miguel Rivera ◽  
Michel C. Nussenzweig ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Steady State ◽  
T Cell ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Class I ◽  
Histocompatibility Complex ◽  
Dc Maturation

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.

scholarly journals A Common Inhibitory Receptor for Major Histocompatibility Complex Class I Molecules on Human Lymphoid and Myelomonocytic Cells

1997 ◽  
Vol 186 (11) ◽  
pp. 1809-1818 ◽  
Author(s):  
Marco Colonna ◽  
Francisco Navarro ◽  
Teresa Bellón ◽  
Manuel Llano ◽  
Pilar García ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
B Cells ◽  
Mhc Class I ◽  
Killer Cell ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Myelomonocytic Cells ◽  
Mhc Class I Molecules

Natural killer (NK) cell–mediated lysis is negatively regulated by killer cell inhibitory receptors specific for major histocompatibility complex (MHC) class I molecules. In this study, we characterize a novel inhibitory MHC class I receptor of the immunoglobulin-superfamily, expressed not only by subsets of NK and T cells, but also by B cells, monocytes, macrophages, and dendritic cells. This receptor, called Ig-like transcript (ILT)2, binds MHC class I molecules and delivers a negative signal that inhibits killing by NK and T cells, as well as Ca2+ mobilization in B cells and myelomonocytic cells triggered through the B cell antigen receptor and human histocompatibility leukocyte antigens (HLA)–DR, respectively. In addition, myelomonocytic cells express receptors homologous to ILT2, which are characterized by extensive polymorphism and might recognize distinct HLA class I molecules. These results suggest that diverse leukocyte lineages have adopted recognition of self–MHC class I molecules as a common strategy to control cellular activation during an immune response.

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