CROSS-REACTIONS BETWEEN THE CYTOTOXIC T-LYMPHOCYTE RESPONSES OF HUMANIMMUNODEFICIENCY VIRUS-INFECTED AFRICAN AND EUROPEAN PATIENTS

The great variability of protein sequences from human immunodeficiency virus (HIV) type 1 (HIV-1) isolates represents a major obstacle to th e development of an effective vaccine against this virus. The surface protein (Env), which is the predominant target of neutralizing antibod ies, is particularly variable. Here we examine the impact of variabili ty among different HIV-1 subtypes (clades) on cytotoxic T-lymphocyte ( CTL) activities, the other major component of the antiviral immune res ponse. CTLs are produced not only against Env but also against other s tructural proteins, as well as some regulatory proteins, The genetic s ubtypes of HIV-1 were determined for Env and Gag from several patients infected either in France or in Africa. The cross-reactivities of the CTLs were tested with target cells expressing selected proteins from HIV-1 isolates of clads A or B or from HIV type 2 isolates. All Africa n patients were infected with viruses belonging to clade A for Env and for Gag, except for one patient who was infected with a clade A Env-c lade G Gag recombinant virus. All patients infected in France were inf ected with clade B viruses. The CTL responses obtained from all the Af rican and all the French individuals tested showed frequent cross-reac tions with proteins of the heterologous clade, Epitopes conserved betw een the viruses of clades A and B appeared especially frequent in Gag p24, Gag p18, integrase, and the central region of Nef. Cross-reactivi ty also existed among Gag epitopes of clades A, B, and G, as shown by the results for the patient infected with the clade A Env-clade G Gag recombinant virus. These results show that CTLs raised against viral a ntigens from different clades are able to cross-react, emphasizing the possibility of obtaining cross-immunizations for this part of the imm une response in vaccinated individuals.