scholarly journals Peptide Immunization Elicits Polyomavirus-Specific MHC Class Ib-Restricted CD8 T Cells in MHC Class Ia Allogeneic Mice

2013 ◽  
Vol 26 (1) ◽  
pp. 109-113 ◽  
Author(s):  
Amelia R. Hofstetter ◽  
Brian D. Evavold ◽  
Aron E. Lukacher
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Mhc Class Ib ◽  
Mhc Class Ia ◽  
Class Ib

scholarly journals Impaired response to Listeria in H2-M3–deficient mice reveals a nonredundant role of MHC class Ib–specific T cells in host defense

2006 ◽  
Vol 203 (2) ◽  
pp. 449-459 ◽  
Author(s):  
Honglin Xu ◽  
Taehoon Chun ◽  
Hak-Jong Choi ◽  
Bin Wang ◽  
Chyung-Ru Wang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Host Defense ◽  
Cd8 T Cells ◽  
Mhc Class Ib ◽  
Cell Responses ◽  
Mhc Class Ia ◽  
Deficient Mice ◽  
Class Ib

The major histocompatibility complex (MHC) class Ib molecule H2-M3 primes the rapid expansion of CD8+ T cells by presenting N-formylated bacterial peptides. However, the significance of H2-M3–restricted T cells in host defense against bacteria is unclear. We generated H2-M3–deficient mice to investigate the role of H2-M3 in immunity against Listeria monocytogenes (LM), a model intracellular bacterial pathogen. H2-M3–deficient mice are impaired in early bacterial clearance during primary infection, with diminished LM-specific CD8+ T cell responses and compromised innate immune functions. Although H2-M3–restricted CD8+ T cells constitute a significant proportion of the anti-listerial CD8+ T cell repertoire, the kinetics and magnitude of MHC class Ia–restricted T cell responses are not altered in H2-M3–deficient mice. The fact that MHC class Ia–restricted responses cannot compensate for the H2-M3–mediated immunity suggests a nonredundant role of H2-M3 in the protective immunity against LM. Thus, the early H2-M3–restricted response temporally bridges the gap between innate and adaptive immune responses, subsequently affecting the function of both branches of the immune system.

scholarly journals An MHC class Ib–restricted CD8 T cell response confers antiviral immunity

2008 ◽  
Vol 205 (7) ◽  
pp. 1647-1657 ◽  
Author(s):  
Phillip A. Swanson ◽  
Christopher D. Pack ◽  
Annette Hadley ◽  
Chyung-Ru Wang ◽  
Iwona Stroynowski ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Mhc Class Ib ◽  
Wild Type ◽  
Mhc Class Ia ◽  
Class Ib

Although immunity against intracellular pathogens is primarily provided by CD8 T lymphocytes that recognize pathogen-derived peptides presented by major histocompatibility complex (MHC) class Ia molecules, MHC class Ib–restricted CD8 T cells have been implicated in antiviral immunity. Using mouse polyoma virus (PyV), we found that MHC class Ia–deficient (Kb−/−Db−/−) mice efficiently control this persistently infecting mouse pathogen. CD8 T cell depletion mitigates clearance of PyV in Kb−/−Db−/− mice. We identified the ligand for PyV-specific CD8 T cells in Kb−/−Db−/− mice as a nonamer peptide from the VP2 capsid protein presented by Q9, a member of the β2 microglobulin–associated Qa-2 family. Using Q9-VP2 tetramers, we monitored delayed but progressive expansion of these antigen-specific CD8αβ T cells in Kb−/−Db−/− mice. Importantly, we demonstrate that Q9-VP2–specific CD8 T cells more effectively clear wild-type PyV than a VP2 epitopenull mutant PyV. Finally, we show that wild-type mice also generate Q9-restricted VP2 epitope–specific CD8 T cells to PyV infection. To our knowledge, this is the first evidence for a defined MHC class Ib–restricted antiviral CD8 T cell response that contributes to host defense. This study motivates efforts to uncover MHC class Ib–restricted CD8 T cell responses in other viral infections, and given the limited polymorphism of MHC class Ib molecules, it raises the possibility of developing peptide-based viral vaccines having broad coverage across MHC haplotypes.

scholarly journals MHC Class Ia Empowers MHC Class Ib-restricted CD8+ T Cells with Strong Tumoricidal Capacity

2021 ◽  
Author(s):  
Yufang Shi ◽  
Qing Li ◽  
Liangyu Lin ◽  
Peishun Shou ◽  
Liu Keli ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Adoptive Transfer ◽  
Priming Effect ◽  
Mhc Class Ib ◽  
Wild Type ◽  
Mhc Haplotype ◽  
Mhc Class Ia ◽  
Class Ib

Abstract The tumoricidal effects of CD8+T cells are well acknowledged, but how MHC Ib-restricted CD8+T (Ib-CD8+T) cells contribute to anti-tumor immunity remains obscure. Here, we show that infusion of MHC Ia+ cells to Kb-/-Db-/- mice induced the expansion of Ib-CD8+T cells in tumors and potently inhibited tumor progression. Such priming of Ib-CD8+T cells by MHC-Ia is not MHC haplotype restricted and MHC Ia tetramers alone can prime Ib-CD8+T cells for activation. The MHC Ia priming promoted Tbet expression in Ib-CD8+T cells and in absence of Tbet, such priming effect diminished. Importantly, these tumoricidal Ib-CD8+T cells are positive for CX3CR1, and exhibit rapid proliferation, high expression of cytotoxic factors, and prolonged persistence at tumor sites. Adoptive transfer of CX3CR1+Ib-CD8+T cells to wild type mice resulted in potent anti-tumor effects. Our findings unravel an uncharacterized function of MHC Ia molecules in immunoregulation and raise the possibility of using Ib-CD8+T cells in tumor immunotherapy.

scholarly journals Induction of M3-Restricted Cytotoxic T Lymphocyte Responses by N-Formylated Peptides Derived from Mycobacterium tuberculosis

2001 ◽  
Vol 193 (10) ◽  
pp. 1213-1220 ◽  
Author(s):  
Taehoon Chun ◽  
Natalya V. Serbina ◽  
Dawn Nolt ◽  
Bin Wang ◽  
Nancy M. Chiu ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Critical Role ◽  
Spleen And Lymph Nodes ◽  
Mhc Class Ia ◽  
Lymphocyte Responses ◽  
Peptide Binding Assay ◽  
Class Ib

Major histocompatibility complex (MHC) class I–restricted CD8+ T cells play a critical role in the protective immunity against Mycobacterium tuberculosis (Mtb). However, only a few Mtb peptides recognized by MHC class Ia–restricted CD8+ T cells have been identified. Information on epitopes recognized by class Ib–restricted T cells is even more limited. M3 is an MHC class Ib molecule that preferentially presents N-formylated peptides to CD8+ T cells. Because bacteria initiate protein synthesis with N-formyl methionine, the unique binding specificity of M3 makes it especially suitable for presenting these particular bacterial epitopes. We have scanned the full sequence of the Mtb genome for NH2-terminal peptides that share features with other M3-binding peptides. Synthetic peptides corresponding to these sequences were tested for their ability to bind to M3 in an immunofluorescence-based peptide-binding assay. Four of the N-formylated Mtb peptides were able to elicit cytotoxic T lymphocytes (CTLs) from mice immunized with peptide-coated splenocytes. The Mtb peptide–specific, M3-restricted CTLs lysed the Mtb-infected macrophages effectively, suggesting that these N-formylated Mtb peptides are presented as the naturally processed epitopes by Mtb-infected cells. Furthermore, T cells from Mtb-infected lungs, spleen, and lymph nodes responded to N-formylated Mtb peptides in an M3-restricted manner. Taken together, our data suggest that M3-restricted T cells may participate in the immune response to Mtb.

scholarly journals Positive selection of MHC class Ib–restricted CD8+ T cells on hematopoietic cells

10.1038/ni814 ◽  
2002 ◽  
Vol 3 (8) ◽  
pp. 772-779 ◽  
Author(s):  
Kevin B. Urdahl ◽  
Joseph C. Sun ◽  
Michael J. Bevan
Keyword(s):  
T Cells ◽  
Positive Selection ◽  
Cd8 T Cells ◽  
Hematopoietic Cells ◽  
Mhc Class Ib ◽  
Class Ib ◽  
Selection Of

scholarly journals H2-M3–Restricted T Cells in Bacterial Infection

1999 ◽  
Vol 190 (2) ◽  
pp. 195-204 ◽  
Author(s):  
Kristen M. Kerksiek ◽  
Dirk H. Busch ◽  
Ingrid M. Pilip ◽  
S. Elise Allen ◽  
Eric G. Pamer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Bacterial Infection ◽  
Primary Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Mhc Class Ib ◽  
Cell Responses ◽  
Mhc Class Ia ◽  
Class Ib

Major histocompatibility complex (MHC) class Ib molecules have been implicated in CD8+ T cell–mediated defenses against intracellular bacterial infection, but the relative importance of MHC class Ib–restricted T cells in antimicrobial immunity is unknown. In this report, we use MHC tetramers to characterize T cell responses restricted by H2-M3, an MHC class Ib molecule that selectively presents N-formyl peptides. We find that sizeable H2-M3–restricted T cell responses, occurring earlier than MHC class Ia–restricted T cell responses, are mounted after primary infection with the intracellular bacterium Listeria monocytogenes. These H2-M3–restricted T cells are cytolytic and produce interferon γ. However, after a second L. monocytogenes infection, H2-M3–restricted memory T cell responses are minor in comparison to the much larger MHC class Ia–restricted responses. This first direct characterization of an MHC class Ib–restricted T cell response indicates that CD8+ T cells responding to L. monocytogenes infection can be divided into two groups: H2-M3–restricted responses, which provide rapid and quantitatively substantial effector function during primary infections but contribute relatively little to memory responses, and MHC class Ia–restricted responses, which expand later during primary infection but form memory T cells that respond rapidly and dramatically in response to subsequent infections by the same pathogen.

scholarly journals Positive selecting cell type determines the phenotype of MHC class Ib-restricted CD8+T cells

2011 ◽  
Vol 108 (32) ◽  
pp. 13241-13246 ◽  
Author(s):  
Hoonsik Cho ◽  
Yaw Bediako ◽  
Honglin Xu ◽  
Hak-Jong Choi ◽  
Chyung-Ru Wang
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Mhc Class Ib ◽  
Cell Type ◽  
Class Ib

MHC class Ia–restricted memory T cells inhibit expansion of a nonprotective MHC class Ib (H2-M3)–restricted memory response

2004 ◽  
Vol 5 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Sara E Hamilton ◽  
Brandon B Porter ◽  
Kelly A Nordyke Messingham ◽  
Vladimir P Badovinac ◽  
John T Harty
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Mhc Class Ib ◽  
Memory Response ◽  
Mhc Class Ia ◽  
Class Ib

scholarly journals MHC Class Ib-Restricted CD8 T Cells Differ in Dependence on CD4 T Cell Help and CD28 Costimulation over the Course of Mouse Polyomavirus Infection

2012 ◽  
Vol 188 (7) ◽  
pp. 3071-3079 ◽  
Author(s):  
Amelia R. Hofstetter ◽  
Mandy L. Ford ◽  
Lucy C. Sullivan ◽  
Jarad J. Wilson ◽  
Annette Hadley ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cell ◽  
Mhc Class Ib ◽  
Cd4 T Cell Help ◽  
Cd28 Costimulation ◽  
T Cell Help ◽  
Class Ib
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