Analysis of antibody specificity against the third variable region of the envelope glycoprotein gp120 of HIV-1 in plasma from HIV-1-positive individuals residing in Brazil

1. Antibody specificity for the principal neutralization domain (PND) of the human immunodeficiency virus type 1 (HIV-1) was studied in plasma from 122 HIV-1-infected individuals residing in Brazil. 2. Using 8 overlapping sequential pentadecapeptides corresponding to the third variable region (V3) of 5 different HIV-1 isolates in an enzyme-linked immunosorbent assay (ELISA), a preferential recognition of the peptides with amino acid sequences corresponding to the HIV-1 isolates IIIB and MN (maximal reactivities of 60-70) compared to the isolates SC, WMJ-2 or RF (maximal reactivities below 60) was observed. 3. A difference was observed in the overall reactivity pattern to HIV-1 SC peptides of plasma collected from individuals residing in the Brazilian states of Rio de Janeiro and Bahia. However, a statistically significant increased recognition by Bahian plasma was only observed for the HIV-1 SC C55 peptide. 4. The mean CD4/CD8 ratio of the group of plasma with an isolate-restricted recognition of peptides (0.522 +/- 0.074) was significantly lower than that of the total group of plasma (1.00 +/- 0.18).

Immunoregulation by processed immunoglobulin on B-cells.

According to Jerne's network hypothesis, the unique amino acid sequences of Ig variable regions, that is, the idiotypic determinants can function in immunoregulatory mechanisms and cellular interactions. Indeed, Id-specific T-cells (mostly CD4+) have since been described, but the nature of Id-positive Ig on B-cells involved in recruiting T-cells is unclear. Studies from our ongoing investigation presented here clearly show that Id can evoke both CD4+ and CD8+ T cells, and exist not only as the integral components of a bona fide antigen-binding receptor Ig but also as distinct molecular entities in processed forms on the cell surface of B-lymphocytes. Using a B-cell hybridoma, 2C3, that expresses anti-hapten (phthalate) antibody receptors on the cell surface, we induced both Id-specific CD4+ and CD8+ T effector cells. The CD4+ T cells were suppressive and mediated generation of Id-loss 2C3 variants, whereas CD8+ T cells were highly cytotoxic and selectively eliminated 2C3 cells both in vitro and in vivo. These effector cells could be induced by cell membrane-associated Ig but not by its soluble form, secreted by 2C3 cells. Antibodies to MHC class I but not class II molecules were inhibitory to this induction. Furthermore, brefeldin A (BFA), an inhibitor of MHC class I mediated processing, blocked induction of CTL but had no effect on the expression of membrane Ig. Moreover, chloroquine, an inhibitor of class II-mediated processing, had no effect. A few reports have recently appeared indicating that an exogenous Ig can be processed by B-cells in the context of MHC class II proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Wa idiotype in seropositive rheumatoid arthritis

Antibodies against cross-reactive idiotypes (CRIs) may prove useful as phenotypic tracers of immunoglobulin variable region genes (VH or VL). CRIs of human rheumatoid factors (RFs) seem to be useful in the elucidation of the incidence and structural characteristics of the latter. Anti-Wa CRI antibodies were produced and an enzyme immunoassay was developed to test polyclonal RFs isolated from sera of 20 rheumatoid arthritis (RA) patients, 7 males and 13 females, aged 17 to 74 years. Seventeen patients had clinically active disease and three were in remission. Disease duration ranged from 1 to 25 years and RF titers ranged from 1:160 to 1:640. The immunoassay could detect as little as 8 ng of a monoclonal purified WaRF and positive results were found in 30 per cent of patient sera. Therefore, we may conclude that at least part of the RFs seen in RA patients derives from germ line genes