PMID- 10501838
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20190831
IS  - 0093-7711 (Print)
IS  - 0093-7711 (Linking)
VI  - 49
IP  - 11-12
DP  - 1999 Oct
TI  - Absence of MHC class II gene expression in a patient with a single amino acid
      substitution in the class II transactivator protein CIITA.
PG  - 957-63
AB  - We investigated the underlying genetic defect in an immunodeficient patient who
      presented with recurrent bacterial infections in his late twenties and
      demonstrated a transcriptional defect in major histocompatibility complex (MHC)
      class II regulation. Transient heterokaryon analysis implicated functional loss
      of CIITA, the MHC class II transactivator protein, and in support of this MHC
      class II antigen expression was restored by stable transfection with the
      wild-type molecule. A single amino acid substitution, phenylalanine to serine, in
      the COOH-terminal portion of the CIITA sequence correlated with reduced
      transcription of both classical (HLA-DP, -DQ, and -DR) and nonclassical (HLA-DM
      and -DO) class II genes. The long survival of the patient, although remarkable,
      was not associated with partial CIITA function as evidenced by residual MHC class
      II expression. These data define at high resolution a region of CIITA that is
      essential for function in both professional and nonprofessional antigen
      presenting cells and which could potentially constitute a target for therapeutic 
      intervention by novel factors with a propensity to downregulate MHC class II
      antigen expression.
FAU - Quan, V
AU  - Quan V
AD  - Department of Nephrology, Guy's, King's and St Thomas' School of Medicine,
      London, UK.
FAU - Towey, M
AU  - Towey M
FAU - Sacks, S
AU  - Sacks S
FAU - Kelly, A P
AU  - Kelly AP
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (HLA-D Antigens)
RN  - 0 (MHC class II transactivator protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - Adult
MH  - *Amino Acid Substitution
MH  - Bacterial Infections/etiology
MH  - Cell Line, Transformed/immunology
MH  - Fatal Outcome
MH  - *Gene Expression Regulation
MH  - *Genes, MHC Class II
MH  - Genetic Complementation Test
MH  - Genetic Predisposition to Disease
MH  - HLA-D Antigens/*genetics/immunology
MH  - Humans
MH  - Male
MH  - *Nuclear Proteins
MH  - *Point Mutation
MH  - Recurrence
MH  - Severe Combined Immunodeficiency/complications/*genetics
MH  - Trans-Activators/*genetics
MH  - Transcription, Genetic
MH  - Transfection
EDAT- 1999/09/29 00:00
MHDA- 1999/09/29 00:01
CRDT- 1999/09/29 00:00
PHST- 1999/09/29 00:00 [pubmed]
PHST- 1999/09/29 00:01 [medline]
PHST- 1999/09/29 00:00 [entrez]
AID - 90490957.251 [pii]
AID - 10.1007/s002510050579 [doi]
PST - ppublish
SO  - Immunogenetics. 1999 Oct;49(11-12):957-63. doi: 10.1007/s002510050579.