An improved assay is described where a surface is provided with immobilized anti-Ig antibodies rather than antigen and where specific antibody-secreting cells (ASC) are detected using soluble antigen probes containing one of several possible labels. The method gives improved sensitivity with less background and is also more representative because antigen binding does not employ immobilized antigen. The assay is particularly effective for measuring antibody secreting cells against HIV, for determining whether an infection is acute as opposed to old or latent, for mapping epitopes and for measuring for ASCs against different antigens in the same reaction.