Maturation of Qa-1b class I molecules requires beta 2-microglobulin but is TAP independent.
Two conformationally distinct and stable forms of Qa-1b, one strongly associated with beta 2-microglobulin (beta 2m) and the other associated with a novel molecule, gp44, were observed during immunochemical studies on the expression of Qa-1b molecules in mouse spleen cells. Both forms are efficiently processed and expressed at the cell surface. However, a large proportion of Qa-1b was found to be disulfide linked to gp44 without any detectable beta 2m. In TAP1-deficient mice, both forms undergo carbohydrate processing and are expressed on the cell surface, suggesting that they may traffic using a pathway not requiring a TAP association step. Consistent with this, size exclusion chromatography of newly synthesized class I molecules shows that high molecular mass complexes containing H-2Kk do not contain Qa-1b. Although Qa-1b can be stably expressed without beta 2m, there was no maturation of either form in cells from beta 2m-deficient mice where heavy chains were rapidly degraded. These results suggest that Qa-1b, like most other class I molecules, requires beta 2m for an initial folding step. However, beta 2m is not essential for subsequent processing of Qa-1b molecules.
Robinson
P J
PJ
MRC-CSC, Hammersmith Hospital, Birbeck College, London, United Kingdom. probinso@rpms.ac.uk
Travers
P J
PJ
Stackpoole
A
A
Flaherty
L
L
Djaballah
H
H
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002850:Chromatography, Gel; D006183:H-2 Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008958:Models, Molecular; D011487:Protein Conformation; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000502:physiology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D008565:Membrane Proteins; C032907:Q surface antigens; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D001613:beta 2-Microglobulin