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Children with autoimmune hepatitis have high serum titers of antibodies directed against a 50-kD protein of rat liver endoplasmic reticulum. Affinity-purified anti-50-kD antibodies were used to screen a rat liver cDNA library in lambda GT-11 expression vector. 12 immunopositive clones were obtained. Crossreactivities between fusion proteins of these clones and the 50-kD protein was demonstrated, and four clones were analyzed by restriction mapping, one of them by nucleotide sequencing. Complete identity was found between the restriction maps of two clones (LKMC1 and LKMC2) and that of the 5' end of the rat cytochrome P450 db2. Sequence of a 608-bp fragment of LKMC1 showed complete homology with the rat P450 db2 form. The restriction map of the other two clones (LKMC3 and LKMC4) was identical to that of rat P450 db1. These results suggest that the antigen recognized by LKMA is a P450 of the IID subfamily.

Introduction Routinely monitoring the HIV viral load ( VL ) of people living with HIV ( PLHIV ) on anti‐retroviral therapy ( ART ) facilitates intensive adherence counselling and faster ART regimen switch when treatment failure is indicated. Yet standard VL ‐testing in centralized laboratories can be time‐intensive and logistically difficult in low‐resource settings. This paper evaluates the outcomes of the first four years of routine VL ‐monitoring using Point‐of‐Care technology, implemented by Médecins Sans Frontières ( MSF ) in rural clinics in Malawi. Methods We conducted a retrospective cohort analysis of patients eligible for routine VL ‐ testing between 2013 and 2017 in four decentralized ART ‐clinics and the district hospital in Chiradzulu, Malawi. We assessed VL ‐testing coverage and the treatment failure cascade (from suspected failure (first VL >1000 copies/ mL ) to VL suppression post regimen switch). We used descriptive statistics and multivariate logistic regression to assess factors associated with suspected failure. Results and Discussion Among 21,400 eligible patients, VL ‐testing coverage was 85% and VL suppression was found in 89% of those tested. In the decentralized clinics, 88% of test results were reviewed on the same day as blood collection, whereas in the district hospital the median turnaround‐time for results was 85 days. Among first‐line ART patients with suspected failure (N = 1544), 30% suppressed ( VL <1000 copies/ mL ), 35% were treatment failures (confirmed by subsequent VL ‐testing) and 35% had incomplete VL follow‐up. Among treatment failures, 80% (N = 540) were switched to a second‐line regimen, with a higher switching rate in the decentralized clinics than in the district hospital (86% vs. 67%, p < 0.01) and a shorter median time‐to‐switch (6.8 months vs. 9.7 months, p < 0.01). Similarly, the post‐switch VL ‐testing rate was markedly higher in the decentralized clinics (61% vs. 26%, p < 0.01). Overall, 79% of patients with a post‐switch VL ‐test were suppressed. Conclusions Viral load testing at the point‐of‐care in Chiradzulu, Malawi achieved high coverage and good drug regimen switch rates among those identified as treatment failures. In...

Class I and class II molecules of the major histocompatibility complex present peptides to T cells. Class I molecules bind peptides that have been generated in the cytosol by proteasomes and delivered into the endoplasmic reticulum by the transporter associated with antigen presentation. In contrast, class II molecules are very efficient in the presentation of antigens that have been internalized and processed in endosomal͞lysosomal compartments. In addition, class II molecules can present some cytosolic antigens by a TAP-independent pathway. To test whether this endogenous class II presentation pathway was linked to proteasomemediated degradation of antigen in the cytosol, the N-end rule was utilized to produce two forms of the inf luenza virus matrix protein with different in vivo half-lives (10 min vs. 5 h) when expressed in human B cells. Whereas class I molecules presented both the short-and the long-lived matrix proteins, class II molecules presented exclusively the long-lived form of antigen. Thus, rapid degradation of matrix protein in the cytosol precluded its presentation by class II molecules. These data suggest that the turnover of long-lived cytosolic proteins, some of which is mediated by delivery into endosomal͞ lysosomal compartments, provides a mechanism for immune surveillance by CD4 ؉ T cells.There are important distinctions between the antigen presentation pathways used by class I and class II molecules of the major histocompatibility complex (MHC) (for review, see ref.