2clv
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MHC CLASS I NATURAL MUTANT H-2KBM8 HEAVY CHAIN COMPLEXED WITH BETA-2 MICROGLOBULIN AND PBM8 PEPTIDE
OverviewOverview
We have characterized three different programs of activation for alloreactive CD8 T cells expressing the BM3.3 TCR, their elicitation depending on the characteristics of the stimulating peptide/MHC complex. The high-affinity interaction between the TCR and the K(b)-associated endogenous peptide pBM1 (INFDFNTI) induced a complete differentiation program into effector cells correlated with sustained ERK activation. The K(bm8) variant elicited a partial activation program with delayed T cell proliferation, poor CTL activity and undetectable ERK phosphorylation; this resulted from a low-avidity interaction of TCR BM3.3 with a newly identified endogenous peptide, pBM8 (SQYYYNSL). Interestingly, mismatched pBM1/K(bm8) complexes induced a split response in BM3.3 T cells, with total reconstitution of T cell proliferation but defective generation of CTL activity that was correlated with strong but shortened ERK phosphorylation. Crystal structures highlight the molecular basis for the higher stability of pBM8/K(bm8) compared to pBM1/K(bm8) complexes that exist in two conformers. This study illustrates the importance of the stability of both peptide/MHC and peptide/MHC-TCR interactions for induction of sustained signaling required to induce optimal CTL effector functions. Subtle allelic structural variations, amplified by peptide selection, may thus orient distinct outcomes of alloreactive TCR-based therapies.
About this StructureAbout this Structure
2CLV is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Distinct orientation of the alloreactive monoclonal CD8 T cell activation program by three different peptide/MHC complexes., Auphan-Anezin N, Mazza C, Guimezanes A, Barrett-Wilt GA, Montero-Julian F, Roussel A, Hunt DF, Malissen B, Schmitt-Verhulst AM, Eur J Immunol. 2006 Jul;36(7):1856-66. PMID:16761314
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- Mus musculus
- Protein complex
- Auphan-Anezin, N.
- Barrett-Wilt, G A.
- Guimezanes, A.
- Hunt, D F.
- Malissen, B.
- Mazza, C.
- Montero-Julian, F.
- Roussel, A.
- Schmitt-Verhulst, A M.
- Alloreactivity
- Class i mhc
- Glycoprotein
- H-2kbm8
- Immune response
- Immune system
- Immunoglobulin domain
- Membrane
- Mhc i
- Polymorphism
- Transmembrane