TcR--one or two binding sites

Jerry Woodward woodward at seqanal.mi.uky.edu
Wed Sep 21 11:53:47 EST 1994


wilson erik robert (erikred at ux1.cso.uiuc.edu) wrote:
: markhodes at aol.com (Mark Hodes) writes:

: >Jonathan Sprent in Paul, Ch.3, writes that it's an open question whether
: >TcR has two adjacent binding sites:  one for self MHC and one for foreign
: >peptide or has one binding site for MHC+peptide complex.  Diagrams in
: >Benjamin & Leskowitz (1993), in Paul (1993) ch. 1, and Sprent in Paul,
: >Ch.3, all seem to accept the second view.  Comments?    Mark Hodes
: >(markhodes at aol.com)

: The two separate site idea is an older concept.  If you look at the
: crystal structure of MHC (HLA A2 Bjorkman et al) you see that the peptide
: is nestled in a "clamshell" like structure in the MHC.  It would be
: pretty hard for the T-cell receptor to just contact the peptide at this
: place and only contact the MHC somewhere else.  Of course different
: residues in the T-cell receptor contact MHC and peptide, but they are
: in the same area (site).

: -- 
: |    \   o IO             | "If we do not find     | Erik Wilson              |
: |-----|      o GANYMEDE   |anything pleasant, at   | University of Illinois   |
: |   O |    o EUROPA       |least we will find      | (217) 359-7547           |
: |----/         o CALLISTO |something new" -Voltaire| erikred at uiuc.edu         |

I agree with Erik Wilson that the MHC-peptide complex does not present two
cleanly separable "sites" with which to bind the TCR.  However, the H-Y TCR
transgenic experiments of Von-Boehmer's group indicate that H-Y specific
TCR's induce positive selection of T cells in mice only with the correct
MHC allele, but in the absence of antigen.  This implies that the H-Y specific,MHC restricted TCR can indeed bind MHC in a specific fashion in the absence
of peptide, or perhaps in the presence of irrelevant peptides, with enough
affinity to induce positive selection.  This implies the presence of at 
least two functional binding sites.  Both "sites" must be occupied in order to 
induce T cell activation.

Jerold G. Woodward, Ph.D.
Associate Professor 
Department of Microbiology and Immunology
University of Kentucky Medical Center
Lexington, KY 40536-0084
Phone: (606) 323-5538
FAX: (606) 257-8994
e-mail: woodward at seqanal.mi.uky.edu
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