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Xenogeneic β2-Microglobulin Substitution Affects Functional Binding of MHC Class I Molecules by CD8+ T Cells
- Source :
- The Journal of Immunology. 179:3588-3595
- Publication Year :
- 2007
- Publisher :
- The American Association of Immunologists, 2007.
-
Abstract
- NK cells and CD8+ T cells bind MHC-I molecules using distinct topological interactions. Specifically, murine NK inhibitory receptors bind MHC-I molecules at both the MHC-I H chain regions and β2-microglobulin (β2m) while TCR engages MHC-I molecules at a region defined solely by the class I H chain and bound peptide. As such, alterations in β2m are not predicted to influence functional recognition of MHC-I by TCR. We have tested this hypothesis by assessing the capability of xenogeneic β2m to modify the interaction between TCR and MHC-I. Using a human β2m-transgenic C57BL/6 mouse model, we show that human β2m supports formation and expression of H-2Kb and peptide:H-2Kb complexes at levels nearly equivalent to those in wild-type mice. Despite this finding, the frequencies of CD8+ single-positive thymocytes in the thymus and mature CD8+ T cells in the periphery were significantly reduced and the TCR Vβ repertoire of peripheral CD8+ T cells was skewed in the human β2m-transgenic mice. Furthermore, the ability of mouse β2m-restricted CTL to functionally recognize human β2m+ target cells was diminished compared with their ability to recognize mouse β2m+ target cells. Finally, we provide evidence that this effect is achieved through subtle conformational changes occurring in the distal, peptide-binding region of the MHC-I molecule. Our results indicate that alterations in β2m influence the ability of TCR to engage MHC-I during normal T cell physiology.
- Subjects :
- Ovalbumin
Protein Conformation
T cell
Immunology
Mice, Transgenic
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Biology
Major histocompatibility complex
Immunophenotyping
Mice
Antigen
Antigens, Heterophile
MHC class I
medicine
Animals
Humans
Immunology and Allergy
Cytotoxic T cell
Mice, Knockout
Antigen Presentation
Beta-2 microglobulin
Egg Proteins
T-cell receptor
H-2 Antigens
Peptide Fragments
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Amino Acid Substitution
biology.protein
beta 2-Microglobulin
CD8
Protein Binding
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 179
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....aa8e503b2522040fd479ec00a736ea2e