HLA class I expression depends on the formation of a peptide-loading complex composed of class I heavy chain; ␤ 2 -microglobulin; the transporter associated with antigen processing (TAP); and tapasin, which links TAP to the heavy chain. Defects in TAP result in a class I deficiency called the type I bare lymphocyte syndrome (BLS). In the present study, we examined a subject with a novel type I BLS who does not exhibit apparent TAP abnormalities but who has a tapasin defect. The subject's TAPASIN gene has a 7.4-kilobase deletion between introns 3 and 7; an Alu repeat-mediated unequal homologous recombination may be the cause of the deletion. No tapasin polypeptide was detected in the subject's cells. IntroductionType I bare lymphocyte syndrome (BLS) is characterized by the lack of cell surface HLA class I. 1,2 Patients with this syndrome showed a reduced number of CD8 ϩ T cells and the lack of natural killer (NK) activities. 3,4 Type I BLS is caused by a deficiency in the transporter associated with antigen processing (TAP). 4-7 TAP transports peptides from the cytoplasm into the inner lumen of the endoplasmic reticulum (ER), and defects in TAP induce poor peptide loading on class I heavy chains (HCs), resulting in a reduction in the number of mature class I molecules on the cell surface. Peptide binding of HCs occurs on the ER by the formation of a complex that is composed of HCs, ␤ 2 -microglobulin, TAP, and tapasin. 8 Tapasin is a 48-kd transmembrane protein that has 2 immunoglobulinlike domains and the ER-retention motif. 9,10 The TAPASIN gene is located at the HLA region. 11 Tapasin binds with TAP, forms a bridge between TAP and HCs, enhances peptide loading, and retains immature HCs in the ER. 12,13 The importance of tapasin in the class I assembly has been indicated by studies using a human mutant cell line, 721.220, which has a truncated tapasin by aberrant splicing. 9,14 TAPASIN-gene-targeted mice had an impaired class I assembly, reduced level of cell surface class I expression, and impaired immune responses. 15,16 Here we analyzed a subject with a novel type I BLS who did not manifest the symptoms commonly observed in TAP-deficient subjects and found that the subject has tapasin deficiency. Study design AntibodiesAntitapasin (peptides at 313-330) and anti-TAP1 rabbit antibodies 5 were provided by K. Tanaka Cell preparationsPeripheral blood mononuclear cells (PBMCs) were isolated from a subject S.M. The B-cell line SM-LCL was established from the patient's PBMCs. The TAP1-deficient KMW-B2 cells have been described previously. 5 Polymerase chain reaction amplification and sequencingGenomic DNA and complementary DNA (cDNA) were prepared as described previously. 5 DNA sequencing was performed by means of ABI 310 (PE Applied Biosystems, Foster City, CA). Flow cytometric analysisCells were stained by fluorescein isothiocyanate (FITC)-conjugated antibodies and analyzed by means of EPICS Elite flow cytometer (Beckman Coulter, Fullerton, CA) Results and discussion S.M. was a 54-year-old woman suffering fr...

To study the role of renal prostaglandins (PGs) in renovascular hypertension, PGE₂ and PGF_2α concentrations in both inner and outer medullae of the kidney were measured by radioimmunoassay in rabbits with hypertension produced by left renal artery constriction. In the acute phase, a week after the surgery, PGE₂ in the inner and outer medullae and PGF_2α in the inner medulla were significantly increased in both the constricted and opposite kidneys (p < 0.01). In chronic phase, 5 weeks after surgery, PGs returned to normal concentrations with the exceptions of PGE₂ in the outer medulla and PGF_2α in the inner medulla of the constricted kidney. These results suggest that increased renal PGs may not be the cause of hypertension but a defensive reaction to renal ischemia, hypertension and sodium load.

The levels of prostaglandins (PGS) E₂ and F₂α in different parts of the rabbit kidney were determined to observe the effect of sodium and indomethacin. After the pretreatment with injections of saline or with indomethacin, tissues from inner and outer medulla and cortex were separated, extracted, analyzed for PGE₂ and PGF₂α by radioimmunoassay. In the normal rabbit kidney, the greatest amount of PG was found in the inner medulla. Saline injections appeared to increase PGE₂ (but not PGF₂α), especially in the inner medulla. Repeated injections of saline, on the other hand, markedly reduced PGE₂ in the inner medulla but increased outer medullary PGE₂. Indomethacin reduced the production of PGS in all kidney segments. These results suggest the bidirectional effect of sodium on PG concentration in the rabbit kidney. Acute administration of sodium may directly stimulate the synthesis of PGE₂ in the inner medulla but chronic stimulation with sodium may alter the pattern of PGE₂ synthesis.

A 22-year-old man was hospitalized because of hypertension, hypokalemic alkalosis and suppressed plasma renin activity. Although these findings were similar to hyperaldosteronism, plasma aldosterone concentration and urinary aldosterone excretion were lower than the normal range. Adrenocortical function also was normal except for aldosterone. Treatment with spironolactone, salt restriction and potassium supplementation improved the hypokalemia but not the hypertension. Blood pressure decreased markedly after administration of triamterene.