Major Histocompatibility Complex MHC Protein Structure & Function
Channel: Eric Martz
Date: 17/07/2020

MHC Classes I and II, molecular structures and how they support defense functions. TALKING TOO SLOWLY? Click the YouTube settings gearwheel and increase playback speed. (To help with watching this you might like an introduction to how protein molecules are shown by computers: http://proteopedia.org/w/Introduction_to_molecular_visualization )
 
CONTENTS
- Main functions of MHC classes I and II with CD8 and CD4 T lymphocytes.
- Cells expressing each class of MHC.
- Sources of peptides in the proteasome and lysosome.
- Reduction of MHC I on virus-infected cells inviting Natural Killer Cells.
- Severe immunodeficiency resulting from genetic absence of MHC II.
- Structure of MHC class I: Alpha chain and domains, beta-2 microglobulin, peptide in cleft with closed ends, papain cleavage locus, CD8 binding site, secondary structure.
- Evolutionary conservation of CD8 binding site and residues binding peptide anchor residues and ends. Variability in sequences of lips of the cleft due to alleles needed to accomodate wide range of peptides.
- Peptide side chains buried (anchor residues) vs. exposed to T cell surveillance.
- Comparison of two different peptides in MHC I from perspective of T cells.
- Structure of MHC class II: Alpha and beta chains, peptide in cleft with open ends.

QUESTIONS AND ANSWERS
- Quiz with immediate feedback: http://proteopedia.org/w/User:Eric_Martz/MHC_Quiz
- Worksheet with open-ended questions for discussion: http://molviz.org/mhc/MHC-questions.pdf
- Suggestions for teachers: http://molviz.org/mhc/MHC-teachers.pdf

LINKS
Terms linked in the tutorial mostly go to Wikipedia. Also:
- CD8 binding site location: https://pubmed.ncbi.nlm.nih.gov/9806638/
- Anchor residues: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC42241/
- Lengths of peptides: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355494/
- MHC deficiencies: https://ghr.nlm.nih.gov/condition/bare-lymphocyte-syndrome-type-i and
https://ghr.nlm.nih.gov/condition/bare-lymphocyte-syndrome-type-ii
 
AUTHORS
- Eric Martz, http://Martz.MolviZ.Org
- Frieda Reichsman, http://MoleculesInMotion.com
 
Molecular structures shown in this tutorial:
 - Mouse MHC I H-2Kb with Sendai virus nucleoprotein nonapeptide: 2vab*; and with vesicular stomatitis virus nucleoprotein octapeptide: 2vaa*.
 - Human MHC II HLA-DR1 with 13 amino acid peptide from influenza hemagglutinin: 1dlh*.
 *Four-character Protein Data Bank codes can be visualized with authors using http://FirstGlance.Jmol.Org
 
Interactive tutorials on DNA, Hemoglobin, Lipid Bilayers and a Membrane Channel, Collagen, the Lac Repressor, and many others are available at http://MolviZ.Org