1. Structure and Function of Proteins Lecturer: Dr. Ora Furman 26-27 Oct 2009 Winter 2009/2010 Teaching Assistants: Sivan Pearl Miriam Oxsman

2. The HLA System The HLA System (i)  HLA: Human Leukocyte Antigen  This human version of MHC molecules presents pathogen-derived peptides to T-cells.  Immune HLA genes: oClass I (HLA-A/B/C) Expressed by most somatic cells. Used for cell-to-T-cells communication. oClass II (HLA-D) Expressed by B-cells, activated T-cells, MΦ, DCs and thymic endothelium. Used for communication among cells of the immune system (T-helper cells stimulation).

3. The HLA System The HLA System (ii)  HLA genes are extremely polymorphic.  Class I and II differ in structure and function. # of different proteinsHLA-I allele* 681HLA-A 1165HLA-B 431HLA-C * Adopted from: http://www.ebi.ac.uk/imgt/hla/stats.html

4. The HLA System The HLA System (iii) Class I vs. class II structure: Adopted from: Klein et. al, N Engl J Med. (2000);343(10):702-9.

5. The HLA System The HLA System (iv) Adopted from: Klein et. al, N Engl J Med. (2000);343(10):702-9. (fig. 5). HLA-peptide interactions:  Class I groove accommodates 7 to 15 residues long peptides.  An HLA class I molecule has 6 pockets along the groove, 2 or 3 determine peptide specificity.  Particular allele product binds thousands of ligands.

6. Superimposition Adopted from: Klein et. al, N Engl J Med. (2000);343(10):702-9. (fig. 5). One molecule is rotated and translated to fit the other with minimal RMS RMS = Root Mean Square (of the distances between the atoms)

7. Homework I Question 1 Please send the figure by email to Sivan Question 2 Rehearse some basic facts that regard interactions. You can look at the introductions of the course’ books (see course’ website for the booklist).website Look at the presentation from the 1 st lesson and try to think of all possible AA-AA interactions [Hydrophobic, ionic and H-bonds (disregard donor/acceptor issues)]. SUBMIT IN PAIRS !

8. Homework II Question 2 – cont. Use PDB and sPDBv to find the neighbors of positions 2 and 9 in both molecules. Elaborate on the way in which a certain trait of the peptide’s AA might effect its neighbors’ identity: compare the neighbors of position 2 in the 1 st molecule to the neighbors of position 2 in the 2 nd ; the same for position 9.