MHC Structure

4. MHC Class I

MHC Class I consists of two chains, a large alpha chain and a smaller beta chain, called beta-2 microglobulin. Alleles code for variations in the alpha chain. All alleles share the same invariant beta chain, whose gene is outside the MHC. The crystallographic structure is known only for the extracellular domains, which were solubilized by cleavage with papain. The transmembrane and cytoplamic domains are not shown because their structures are not known.

Polypeptide chains of MHC I.
Alpha Chain,
Beta Chain,
Antigenic Peptide.

Domain structure of MHC I.
Antigenic Peptide,
Alpha chain, domain 1,
Alpha chain, domain 2,
Alpha chain, domain 3,
Beta₂ Microglobulin,
Disulfide bonds,
Papain cleavage locus.

Details: Origin of the Peptide?

Labels

CD8 is a T cell co-receptor that is crucial for effective immune responses by T cells to foreign peptides presented by MHC I. CD8 binds directly to MHC I.
CD8 binding site (white).

Details: CD8 Binding Site

A spacefilling view shows the shape of the molecule.

Secondary structure: Alpha Helix, Beta Strand, Coil.

Evolutionary conservation (alpha chain). The CD8-binding loop is marked with white halos.
Antigenic Peptide.

Details: Technical

Immunoglobulin-like domains: Beta₂ microglobulin and the Alpha 3 domain are protein domains with immunoglobulin-like structure (Ig superfamily domains). Such domains are widely used building blocks that are found in many proteins with different functions. Each Ig domain consists of two small beta sheets connected with a disulfide bond. For more about immunoglobulin domain structure, please see the tutorial on Antibody.

What Do You See?

What does "MHC" stand for?
How many polypeptide chains make up an MHC Class I molecule, not counting the antigenic peptide?
How many polypeptide chains make up the MHC I peptide-binding cleft, not counting the antigenic peptide?
Does beta₂ microglobulin touch the rest of the MHC I molecule?
Which chain of MHC I is invariant?
Which MHC I domains have immunoglobulin-like structure?
Which end of the MHC I molecule is anchored to the cell membrane?
What region of MHC I is least conserved, when multiple sequences are compared in an evolutionary conservation analysis? Why?
Does CD8 bind to an evolutionarily variable or conserved region of MHC I? What two amino acids in the binding region are most highly conserved?

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Explore further the molecule(s) in this Tutorial:

Glycine: glycine.pdb in FirstGlance in Jmol. This molecule appears in Chapter 1. This molecule is not available, at least in the form shown here, from the PDB.
Quadrapeptide KAIT (from 1rog): pepb27_4.pdb in FirstGlance in Jmol. This molecule appears in Chapter 2. This molecule is not available, at least in the form shown here, from the PDB.
Disulfide bond between 2 pentapeptides (from 2ig2): s-s.pdb in FirstGlance in Jmol. This molecule appears in Chapter 3. This molecule is not available, at least in the form shown here, from the PDB.
Mouse MHC Class I (H-2K^b) with nonapeptide from Sendai virus nucleoprotein: 2vab in Proteopedia or in FirstGlance in Jmol. This molecule appears in Chapters 4, 5, 6.
Mouse MHC Class I (H-2K^b) with octapeptide from VSV nucleoprotein: 2vaa in Proteopedia or in FirstGlance in Jmol. This molecule appears in Chapter 6.
Both virus peptides, compared: pepboth.pdb in FirstGlance in Jmol. This molecule appears in Chapter 6. This molecule is not available, at least in the form shown here, from the PDB.
Human MHC Class II (HLA-DR1) with 13 amino acid peptide from influenza hemagglutinin: 1dlh in Proteopedia or in FirstGlance in Jmol. This molecule appears in Chapter 7.

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This Tutorial is copyright © 2010 by Eric Martz, and is licensed under a Creative Commons Attribution - Noncommercial - Share Alike 3.0 License. Copies of this Tutorial are available on request from the author, should you wish to put it on your own server, or modify the content.

History This tutorial was first developed as a RasMol Movie Script in December, 1995. In November, 1997, it was ported to a "Two Frame Chime Tutorial", and some improvements were made in early 1998. In August, 2010, it was ported to Jmol with further improvements.
[JTAT version: September 8, 2010.]