PMID- 16648140
OWN - NLM
STAT- MEDLINE
DCOM- 20060918
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 27
DP  - 2006 Jul 7
TI  - Defective human leukocyte antigen class I-associated antigen presentation caused 
      by a novel beta2-microglobulin loss-of-function in melanoma cells.
PG  - 18763-73
AB  - The major histocompatibility complex class I molecules consist of three subunits, 
      the 45-kDa heavy chain, the 12-kDa beta(2)-microglobulin (beta(2)m), and an 
      approximately 8-9-residue antigenic peptide. Without beta(2)m, the major 
      histocompatibility complex class I molecules cannot assemble, thereby abolishing 
      their transport to the cell membrane and the subsequent recognition by 
      antigen-specific T cells. Here we report a case of defective antigen presentation 
      caused by the expression of a beta(2)m with a Cys-to-Trp substitution at position 
      25 (beta(2)m(C25W)). This substitution causes misfolding and degradation of 
      beta(2)m(C25W) but does not result in complete lack of human leukocyte antigen 
      (HLA) class I molecule expression on the surface of melanoma VMM5B cells. Despite 
      HLA class I expression, VMM5B cells are not recognized by HLA class I-restricted, 
      melanoma antigen-specific cytotoxic T lymphocytes even following loading with 
      exogenous peptides or transduction with melanoma antigen-expressing viruses. 
      Lysis of VMM5B cells is restored only following reconstitution with exogenous or 
      endogenous wild-type beta(2)m protein. Together, our results indicate impairment 
      of antigenic peptide presentation because of a dysfunctional beta(2)m and provide 
      a mechanism for the lack of close association between HLA class I expression and 
      susceptibility of tumor cells to cytotoxic T lymphocytes-mediated lysis in 
      malignant diseases.
FAU - Chang, Chien-Chung
AU  - Chang CC
AD  - Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263, 
      USA.
FAU - Ogino, Takeshi
AU  - Ogino T
FAU - Mullins, David W
AU  - Mullins DW
FAU - Oliver, Janine L
AU  - Oliver JL
FAU - Yamshchikov, Galina V
AU  - Yamshchikov GV
FAU - Bandoh, Nobuyuki
AU  - Bandoh N
FAU - Slingluff, Craig L Jr
AU  - Slingluff CL Jr
FAU - Ferrone, Soldano
AU  - Ferrone S
LA  - eng
GR  - P30 CA160056/CA/NCI NIH HHS/United States
GR  - R01 CA57653/CA/NCI NIH HHS/United States
GR  - R01 CA67108/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060428
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-A Antigens)
RN  - 0 (beta 2-Microglobulin)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Antigen Presentation/*genetics
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Cytotoxicity, Immunologic
MH  - Down-Regulation/immunology
MH  - Gene Expression Regulation, Neoplastic/immunology
MH  - Genes, MHC Class I/*immunology
MH  - HLA-A Antigens/*genetics/immunology
MH  - Humans
MH  - Melanoma/genetics/*immunology
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - beta 2-Microglobulin/*genetics/immunology
EDAT- 2006/05/02 09:00
MHDA- 2006/09/19 09:00
CRDT- 2006/05/02 09:00
PHST- 2006/05/02 09:00 [pubmed]
PHST- 2006/09/19 09:00 [medline]
PHST- 2006/05/02 09:00 [entrez]
AID - S0021-9258(20)57640-0 [pii]
AID - 10.1074/jbc.M511525200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Jul 7;281(27):18763-73. doi: 10.1074/jbc.M511525200. Epub 2006 
      Apr 28.