Epitopes recognized by the neutralizing antibodies of an HIV-1-infected individual.

Sera from individuals infected by HIV-1 usually neutralize multiple viral isolates. To determine the extent to which these neutralizing antibodies recognize a principal neutralizing determinant in the V3 region of the envelope protein gp120 (amino acids 308-332), one broadly neutralizing serum was fractionated by affinity chromatography on immobilized peptide columns. Antibodies that neutralize one isolate (HTLV-IIIMN) were substantially but not completely absorbed by the peptide corresponding to a portion of its V3 determinant, whereas the antibodies that neutralize two other isolates (HTLV-IIIB and HTLV-IIIRF) were not absorbed by homologous peptides corresponding to their neutralizing determinants. Neutralizing antibodies also failed to be absorbed by full length envelope protein gp160 and by two other envelope peptides previously reported to be broadly neutralizing epitopes (amino acids 254-274 and 735-752). We conclude that the infected individual had raised a type-restricted neutralizing response targeted at a linear epitope in the V3 region, and that broad neutralization resulted from recognition of epitopes not yet identified.

Principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein.

The principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) is located in the external envelope protein, gp120, and has previously been mapped to a 24-amino acid-long sequence (denoted RP135). We show here that deletion of this sequence renders the envelope unable to elicit neutralizing antibodies. In addition, using synthetic peptide fragments of RP135, we have mapped the neutralizing determinant to 8 amino acids and found that a peptide of this size elicits neutralizing antibodies. This sequence contains a central Gly-Pro-Gly that is generally conserved between different HIV-1 isolates and is flanked by amino acids that differ from isolate to isolate. Antibodies elicited by peptides from one isolate do not neutralize two different isolates, and a hybrid peptide, consisting of amino acid sequences from two isolates, elicits neutralizing antibodies to both isolates. By using a mixture of peptides of this domain or a mixture of such hybrid peptides the type-specificity of the neutralizing antibody response to this determinant can perhaps be overcome.

Glucagon, insulin, growth hormone, and glucose concentrations in blood plasma of lactating dairy cows.

Concentrations of glucose, growth hormone, insulin, and glucagon in blood plasma relative to days in milk, milk production, type of housing, and season were measured. Blood samples were obtained from 133 to 150 lactating Holstein cows on 3 consecutive days in July, October, January, and April. Glucose, insulin, and ratio of insulin to glucagon increased with increasing days in milk. Growth hormone and ratio of growth hormone to insulin decreased with increasing days in milk. Glucagon concentrations were similar throughout lactation. Above average milk production throughout lactation was associated with above average glucagon, lower insulin, and lower glucose. The relationship was not significant between growth hormone concentration and milk production, however. Cows on summer pasture with limited grain supplement had higher growth hormone and lower glucose, insulin, and glucagon than cows eating ad libitum in barns or feedlot. In general, however, all cows had higher glucose and lower growth hormone, insulin, and ratio of insulin to glucagon in July than in cooler months.