Kinetics and Specificities of the T Helper–Cell Response to GP120 in the Asymptomatic Stage of HIV–1 Infection

Abstract

Geretti AM, Van Baalen CA, Borleffs JCC, van Els CACM, Osterhaus ADME. Kinetics and Specificities ofthe T Helper-Cell Response togpl20 in the Asymptomatic Stage of HIV-1 Infection. Scand J Immunol 1994:39:355-62 Peripheral blood mononuclear cells from 36 asymptomatic HIV-1 seropositive individuals were tested longitudinally for in vitro T-cell proliferation and IL-2 production in response to synthetic peptides spanning the entire gp 120 of HIV-1. At baseline, significant T-cell proliferation to pooled and individual peptides was observed in 15 ofthe 36 donors. After 12 months, proliferative responses to peptide pools were lost or decreased significantly in most donors. Responses appeared to fluctuate over time: at 12 months new recognition sites were detected in four of 10 donors showing T-cell proliferation at baseline, as well as in five of 15 donors with no previous proliferative responses. IL-2 production appeared to be a more sensitive and longer preserved parameter of T-helpter cell function: at baseline tbe majority of donors with no T-cell proliferation produced IL-2 in response to pooled peptides. Tbis response was not decreased significantly after 12 months. Tbe overall patterns of response to both pooled and individual peptides were heterogeneous among donors. Multiple recognition sites were detected in both variable and conserved regions of gpl20, but no pool or individual peptide was recognized by all responders. Functional T-cell responses were not statistically correlated to CD4+ cell percentile and absolute numbers.

HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals

“…Furthermore, the presence of significant proUierative responses was not confirmed upon retesting within a 18-montb period in several patients. Fluctuation of proliferative responses to peptides of gpl20 has been recently reported by Geretti et al [17]. who showed bolh loss and appearance of significanl responses in two determinations separated by a 1-year period.…”

Proliferative Responses to Human Immunodeficiency Virus Type 1 (HIV‐1) gp120 Peptides in HIV‐1–Infected Individuals Immunized with HIV‐1 rgp120 or rgp160 Compared with Nonimmunized and Uninfected Controls

“…Once CD4 ϩ epitopes are fully delineated in the context of natural infection, immunotherapy, and viral escape via mutation, potential correlates of protective immunity may be identified and augmented by specific vaccination. Although there are several studies that have examined the proliferative responses to regions of the HIV-1 envelope in natural history cohorts [12][13][14][15][16] and envelope-immunized volunteers [17], we present the first comparative description of HIV-1 envelope proliferative responses in HIV-1-infected volunteers who have undergone repetitive immunization with either rgp120 or rgp160 in phase I clinical trials. Although these phase I trials, using multiple dose and schedule combinations, were not specifically designed for direct comparison, the similarities in the volunteer cohorts and multiple immunizations over relatively long periods invited qualitative comparisons.…”

“…Combined vaccinees Placebo recipients Geretti [13] Mutch [14] Wahren [15] Schrier [16] 152 53 13 11 25 269 50 7 11 38 30-40 443 39 7 0 0 112 36 7 11 25 38 337 33 7 14 13 191 31 0 8 25 319 28 0 3 0 35 391 11 13 3 0 55 454 8 0 11 0 45 99 6 0 3 25 31 variable regions may have limited effects on HIV-1 immunoregulation.…”

“…They do, however, span the entire gp120 LAI/ LAV consensus sequence from the end of the signal sequence until the beginning of the transmembrane sequence of gp41. Disregarding peptide 259, whose sequence is completely contained within peptide 246, the average length of the peptides is ∼29 amino acids (range, 23-40) with an average overlap of 10 amino acids (range, [3][4][5][6][7][8][9][10][11][12][13]. There was typically excellent sequence homology between the immunogens (rgp120 and rgp160) administered in the two trials and the consensus LAI sequence represented in the peptides.…”

Scanning the HIV Genome for CD4+ T Cell Epitopes Restricted to HLA-DP4, the Most Prevalent HLA Class II Molecule

“…In a pioneering study, the env 30 -51 peptide, which includes env 31-45, was recognized by 2 of 15 asymptomatic seropositive responders. However, these responses were not documented for their HLA class II restriction (40).…”