ABSTRACT
Current ideas about DM actions have been strongly influenced by studies of mutant strains expressing the H-2(b) haplotype. To evaluate DM contributions to class II activities in BALB/c mice, we generated a novel mutation at the DMa locus via embryonic stem cell technology. Unlike long-lived A(b)/class II-associated invariant chain-derived peptide (CLIP) complexes, mature A(d) and E(d) molecules are loosely occupied by class II-associated invariant chain-derived peptide and are SDS unstable. BALB/c DM mutants weakly express BP107 conformational epitopes and toxic shock syndrome toxin-1 superantigen-binding capabilities, consistent with partial occupancy by wild-type ligands. Near normal numbers of mature CD4(+) T cells fail to undergo superantigen-mediated negative selection, as judged by TCR Vbeta usage. Ag presentation assays reveal consistent differences for A(d)- and E(d)-restricted T cells. Indeed, the mutation leads to decreased peptide capture by A(d) molecules, and in striking contrast causes enhanced peptide loading by E(d) molecules. Thus, DM requirements differ for class II structural variants coexpressed under physiological conditions in the intact animal.
Subject(s)
CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , Histocompatibility Antigens Class II/immunology , Histocompatibility Antigens Class II/metabolism , Mice, Inbred BALB C/immunology , Peptides/immunology , Peptides/metabolism , Alleles , Animals , Antigen Presentation/genetics , Antigens, Differentiation, B-Lymphocyte/genetics , Antigens, Differentiation, B-Lymphocyte/metabolism , CD4-Positive T-Lymphocytes/metabolism , Cell Differentiation/genetics , Cell Differentiation/immunology , Cell Line , Clone Cells , Crosses, Genetic , Dimerization , Female , Gene Targeting , Haplotypes , Histocompatibility Antigens Class II/chemistry , Histocompatibility Antigens Class II/genetics , Lymphocyte Activation/genetics , Male , Mice , Mice, Inbred BALB C/genetics , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Knockout , Peptides/genetics , Protein Conformation , Sequence Deletion , Sodium Dodecyl SulfateABSTRACT
Equine rhinoviruses (ERVs) are picornaviruses which cause a mild respiratory infection in horses. The illness resembles the common cold brought about by rhinoviruses in humans; however, the presence of a viraemia during ERV-1 infection, the occurrence of persistent infections and the physical properties are all more reminiscent of foot-and-mouth disease virus (FMDV). cDNA cloning and sequencing of the genomes of ERV-1 and ERV-2 between the poly(C) and poly(A) tracts showed that the serotypes are heterogeneous. Nevertheless, the genomic architecture of both serotypes is most similar to that of FMDV. Indeed, a comparison of the derived protein sequences of ERV-1 shows that their identity is greatest to FMDV. In contrast, most ERV-2 proteins are more related to encephalomyocarditis virus (EMCV) proteins than they are to FMDV or ERV-1. These results place ERV-1 alongside FMDV in the aphthovirus genus of the picornavirus family and indicate that this virus may serve as a model system for examining the biology of FMDV.
Subject(s)
Picornaviridae/classification , Amino Acid Sequence , Animals , Aphthovirus/classification , Aphthovirus/genetics , Base Sequence , Capsid/chemistry , Cardiovirus/classification , Cardiovirus/genetics , Cell Line , DNA, Viral , Genome, Viral , Humans , Introns , Molecular Sequence Data , Picornaviridae/genetics , Rabbits , Sequence Homology, Amino Acid , Serotyping , Viral Proteins/geneticsABSTRACT
In 104 malignant melanoma patients who underwent lymphadenectomy (67 females, 37 males), correlations were studied between histologically diagnosed lymph node metastasis, the type of malignant melanoma and the depth of invasion according to Clark, as well as other parameters. In 35.6% of the patients, metastases of the primary tumor were found in one or several regional lymph nodes. In about one third of the patients, the clinical and histological lymph node findings were proven to diverge. The female:male ratio of generally about 2:1 shifted to 1:1 in the group of patients with lymph node metastasis, i.e. cases with lymph node metastasis were found significantly increased in the male sex, and also, when primary tumors were localized on the trunk. A prognostic correlation between the two parameters, sex and localization, is suggested by the high incidence of histologicallly diagnosed metastases in 1 or 2 lymph node regions, when malignant melanomas were localized on the trunk in males. As to the types and the micro-stages of primary tumors, the number of cases collected until now does not permit establishing clear correlations with the incidence of lymph node involvement. Calculating the 5-year-survival rates for patients with and without lymph node metastasis according to the "actuarial method", we found the prognosis to depend largely on the presence or absence of lymph node involvement, even at a time as early as at primary tumor excision. Our results support the indication for prophylactic lymphadenectomy in malignant melanoma, provided the primary tumor has reached or surpassed the micro-stage 3.
