Excess beta 2 microglobulin promoting functional peptide association with purified soluble class I MHC molecules.
T lymphocytes expressing alpha beta receptors recognize antigenic peptide fragments bound to major histocompatibility complex class I or class II molecules present on the surface membranes of other cells. Peptide fragments are present in the two available HLA crystal structures and recent data indicate that peptide is required for the stable folding of the class I heavy chain and maintenance of its association with the class I light chain, beta 2-microglobulin (beta 2m), at physiological temperature. To explain how the exogenous peptide used to create targets for cytotoxic cells bearing CD8 antigen could associate with apparently peptide-filled extracellular class I molecules, we hypothesized that stable binding of exogenous peptide to mature class I molecules reflects either the replacement of previously bound peptide during the well documented beta 2m exchange process or the loading of 'empty' class I heavy chains dependent on the availability of excess beta 2m. In either case, free beta 2m should enhance peptide/class I binding. Using either isolated soluble class I molecules or living cells, we show here that free purified beta 2m markedly augments the generation of antigenic complexes capable of T-cell stimulation.
Kozlowski
S
S
Molecular Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Takeshita
T
T
Boehncke
W H
WH
Takahashi
H
H
Boyd
L F
LF
Germain
R N
RN
Berzofsky
J A
JA
Margulies
D H
DH
D002474:Cell-Free System; D015686:Gene Products, env / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000378:metabolism* / Q000502:physiology
D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D006680:HLA Antigens; D011498:Protein Precursors; D001613:beta 2-Microglobulin